rs201307101

chr14-23417295-C-Achr14-23417295-C-Gchr14-23417295-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 5P and 8B. PM1 PP2 PP3_Moderate BP6_Very_Strong

The NM_000257.4(MYH7):c.4377G>T(p.Lys1459Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000458 in 1,614,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★★). Synonymous variant affecting the same amino acid position (i.e. K1459K) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (0 hom.)
• Consequence: MYH7 NM_000257.4 missense
• Clinical Significance: Likely benign reviewed by expert panel P:4 U:12 B:10
• Conservation: PhyloP100: 1.07

Genes affected

MYH7 (HGNC:7577): (myosin heavy chain 7) Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]

MHRT (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM1: In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 13 uncertain in NM_000257.4
• PP2: Missense variant where missense usually causes diseases, MYH7
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.92
• BP6: Variant 14-23417295-C-A is Benign according to our data. Variant chr14-23417295-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 43012.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr14-23417295-C-A is described in Lovd as [Likely_benign]. Variant chr14-23417295-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH7	NM_000257.4	c.4377G>T	p.Lys1459Asn	missense_variant	32/40	ENST00000355349.4
MHRT	NR_126491.1	n.735C>A		non_coding_transcript_exon_variant	5/6
MYH7	NM_001407004.1	c.4377G>T	p.Lys1459Asn	missense_variant	31/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH7	ENST00000355349.4	c.4377G>T	p.Lys1459Asn	missense_variant	32/40	1	NM_000257.4	P1

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000299 AC: 75 AN: 251252 Hom.: 0 AF XY: 0.000331 AC XY: 45 AN XY: 135806

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000555

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000482 AC: 704 AN: 1461804 Hom.: 0 Cov.: 34 AF XY: 0.000433 AC XY: 315 AN XY: 727206

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000594

Gnomad4 OTH exome AF: 0.000397

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74370

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000341 Hom.: 0

Bravo AF: 0.000242

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000305 AC: 37

EpiCase AF: 0.000491

EpiControl AF: 0.000356

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:4 Uncertain:12 Benign:10

Revision: reviewed by expert panel

Submissions by phenotype

not provided Pathogenic:1 Uncertain:3 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	May 19, 2019	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Oct 12, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 29, 2019	This variant is associated with the following publications: (PMID: 25467552, 21127202, 19150014, 15358028, 22958901, 17125710, 24793961, 26654849, 22765922, 25342278, 23299917, 28381408, 29300372, 25637381, 24093860, 23074333, 23794396, 27247418, 29181379, 30871747, 31006259, 31737537, 30847666, 33297573) -
Likely pathogenic, no assertion criteria provided	clinical testing	Stanford Center for Inherited Cardiovascular Disease, Stanford University	Sep 06, 2012	Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. Based on the strong case data, moderate segregation data, and sufficiently low frequency in general population samples, we consider this variant likely disease causing. In total this variant has been seen in 11 unrelated cases of MYH7-linked phenotypes (including one case in our center), with moderate segregation data in one family. In addition to patients with HCM, there is one patient with Ebstein’s and one patient with borderline hypertrophy with an abnormal papillary muscle anatomy and LVOT obstruction. We have seen this variant in one patient in our center, a Caucasian, non-Hispanic woman diagnosed with HCM at 71 years of age with a murmur first noted at 53 years of age. She underwent myectomy at 73 years of age. This variant was initially reported in one individual with HCM (van Driest et al 2004). That report included only sequencing of MYH7. However, a separate report by the same group reported on the incidence of multiple variants in this cohort after analysis of 9 sarcomere genes and based on that it appears this patient had only this one MYH7 variant (van Driest et al 2004). Ancestry data was not available. Laredo et al (2006) reported the variant in a family from their Spanish cohort, with some evidence of co-segregation; from 9 family members 2 had HCM and were genotype positive for the variant, 1 family member with HCM was not genotyped but was an obligate carrier (Laredo et al 2006). Three additional family members were found to be carriers, they had a normal phenotype (and were in their thirties). Garcia-Castro et al (2009) reported the variant in a single case of HCM from their Spanish cohort who underwent sequencing of 5 sarcomere genes. Given authors and recruitment site, this seems to overlap with a case later reported by Coto et al (2012) but not with the family reported by Laredo et al (2006). Postma et al (2010) reported one individual with this variant with Epstein’s anomaly but no hypertrophy from a cohort recruited in the Netherlands, the UK and Germany (of note, Ebstein's anomaly, often with noncompaction, has recently been associated with MYH7 variants (Budde et al 2007, Postma et al 2011, van Engelen et al 2011)). The Seidman group observed the variant in 1 of 1963 individuals from the Jackson Heart Study who underwent sequencing of eight sarcomere genes (Bick et al 2012). They note the following about that individual's phenotype: 52yo with LVWT 1.1 cm, LVDD 4.64 cm, LAD 4.24 cm, fractional shortening 0.37, 1 physical cardiovascular risk factor (not specified). Marsiglia et al (2014) observed the variant in 3 of 131 Brazilian patients with HCM who underwent sequencing of MYH7, MYBPC3, and TNNT2. Ackerman's group observed the variant in 2 patients in their cohort of 1053 unrelated patients with HCM who underwent DHLPC-based analysis of 9 sarcomere genes at Mayo (Bos et al 2014). Note that these cases likely overlap with prior reports by Ackerman's group (ex. van Driest et al 2004) and there is also a chance they overlap with internal cases from the clinical genetic testing labs. Ancestry data was not reported. Per their ClinVar submission (SCV000059557), LMM considers this variant to be of uncertain significance, based on the atypical presentation in the patient with Ebstein’s (perhaps this was before the MYH7-Ebstein’s link was reported), and the fact that most carriers in the Laredo et al family were mildly affected or unaffected. It also noted that LMM “detected this variant in 3 out of >2000 Caucasian probands, one of whom carried a second, pathogenic variant, and one only had borderline hypertrophy with an abnormal papillary muscle anatomy and LVOT obstruction (no diagnosis was available -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 01, 2014	- -

Hypertrophic cardiomyopathy 1 Pathogenic:1 Uncertain:2 Benign:1

Likely pathogenic, criteria provided, single submitter	clinical testing	Laboratory of Genetics and Molecular Cardiology, University of São Paulo	-	- -
Uncertain significance, criteria provided, single submitter	research	Agnes Ginges Centre for Molecular Cardiology, Centenary Institute	Dec 17, 2014	This MYH7 Lys1459Asn variant was first reported by Van Driest SL, et al. (2004) as a novel variant in one HCM idex case. It has since been identified in other HCM patients (Laredo R, et al., 2007; García-Castro M, et al., 2009; Marsiglia JD, et al., 2013), and has also been identified in one sporadic case of Ebstein anomaly (Postma AV, et al., 2011). Segregation analysis by Laredo R, et al. (2007) identified 4 family members of the index case to be carriers of the MYH7 Lys1459Asn variant - 1 individual with mild disease; and 3 clinically unaffected family members (all >30 years old). We have identified this variant in 2 unrelated HCM cases, both of whom carry either a second pathogenic or likely pathogenic variant. Segregation analysis in one family did not show this MYH7 Lys1459Asn variant to segregate with disease (3 of 4 clinically affected individuals are not carriers). This variant is present (MAF=0.0003016) in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). Computational tools SIFT predicts this variant to be "deleterious", however, no prediction is called by PolyPhen-HCM. In summary, although this variant is present at a low frequency, weak or no evidence of the variant segregating with disease casts doubt on its role as the primary cause of HCM. We cannot rule out its potential as a modifying variant however, further evidence is required to fully understand its pathogenic role. Thus, we classify this variant as of "unknown significance". -
Likely benign, criteria provided, single submitter	clinical testing	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	May 06, 2021	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely Benign. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established however, missense variants have been proposed to act in a dominant negative manner (PMID: 24714796). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance. Hypertrophic cardiomyopathy is known to be an incompletely penetrant disease, although data specific to this gene is lacking (PMID: 29300372). (I) 0200 - Variant is predicted to result in a missense amino acid change from lysine to asparagine. (I) 0251 - This variant is heterozygous. (I) 0308 - Population frequency for this variant is out of keeping with known incidence of MYH7 -related disease. (SB) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated myosin tail domain (Pfam). (I) 0805 - This variant has strong previous evidence of being benign in unrelated individuals. Although this variant has conflicting interpretations in ClinVar, it has been reviewed as likely benign by the ClinGen expert panel (ClinGen). (SB) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 20, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Cardiomyopathy Uncertain:2 Benign:2

Likely benign, reviewed by expert panel	curation	ClinGen Cardiomyopathy Variant Curation Expert Panel	Dec 15, 2016	The filtering allele frequency of the c.4377G>T (p.Lys1459Asn) variant in the MYH7 gene is 0.0375% (34/66566) of European chromosomes by the Exome Aggregation Consortium (http://exac.broadinstitute.org), which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BS1; PMID:29300372). Additionally, while computational prediction tools and conservation analysis suggest that this variant may impact the protein (PP3), this pathogenic evidence code (PP3) was not considered to be in conflict with a likely benign conclusion given the accuracy of computation prediction tools. In summary, this variant meets criteria to be classified as likely benign for cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): PP3; BS1 -
Uncertain significance, criteria provided, single submitter	clinical testing	All of Us Research Program, National Institutes of Health	Jan 11, 2024	This missense variant replaces lysine with asparagine at codon 1459 of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in multiple individuals affected with hypertrophic cardiomyopathy (PMID: 17125710, 19150014, 22765922, 24793961, 28356264), in an individual affected with Ebstein anomaly (PMID: 21127202), and in an individual affected with dilated cardiomyopathy (PMID: 30871747). This variant has also been identified in 83/282640 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The relatively high frequency of this variant in the general population suggests that this variant is unlikely to be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -
Likely benign, criteria provided, single submitter	clinical testing	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	Dec 07, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Jan 24, 2023	This missense variant replaces lysine with asparagine at codon 1459 of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in multiple individuals affected with hypertrophic cardiomyopathy (PMID: 17125710, 19150014, 22765922, 24793961, 28356264), in an individual affected with Ebstein anomaly (PMID: 21127202), and in an individual affected with dilated cardiomyopathy (PMID: 30871747). This variant has also been identified in 83/282640 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The relatively high frequency of this variant in the general population suggests that this variant is unlikely to be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -

not specified Uncertain:1 Benign:2

Uncertain significance, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 22, 2023	Variant summary: MYH7 c.4377G>T (p.Lys1459Asn) results in a non-conservative amino acid change located in the myosin tail domain (IPR002928) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0003 in 251252 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in MYH7 causing Cardiomyopathy (0.0003 vs 0.0013), allowing no conclusion about variant significance. c.4377G>T has been reported in the literature in multiple individuals affected with cardiomyopathy, including those affected with hypertrophic cardiomyopathy (e.g., VanDriest_2004, Laredo_2006, Gomez_2017, vanLint_2019), dilated cardiomyopathy (e.g., Sousa_2019), long QT syndrome (e.g., Quenin_2017), and an individual with an Ebstein anomaly (Postma_2011). However, these reports do not show strong evidence for causality (e.g., lack of co-segregation data) and therefore do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28356264, 29300372, 17125710, 21127202, 28912206, 30871747, 15358028, 31006259, 30847666). Multiple ClinVar submitters (evaluation after 2014), including the ClinGen Cardiomyopathy Variant Curation Expert Panel, have cited the variant with conflicting assessments (likely benign (including the expert panel), n = 8; VUS, n = 6; benign, n = 1; likely pathogenic, n = 2). The ClinGen Cardiomyopathy Variant Curation Expert Panel states that this variant occurs at a high enough frequency to be classified as likely benign based on their defined thresholds (Kelly_2018). Based on the evidence outlined above, the variant was classified as VUS-possibly benign. -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 11, 2018	p.Lys1459Asn in exon 32 of MYH7: This variant is not expected to have clinical s ignificance because it has been identified in 0.05% (66/126506) of European chro mosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute .org/; dbSNP rs201307101). ACMG/AMP Criteria applied: PP3; BS1. -
Likely benign, criteria provided, single submitter	clinical testing	Blueprint Genetics	May 25, 2015	- -

Primary familial hypertrophic cardiomyopathy Pathogenic:1 Uncertain:1

Uncertain significance, criteria provided, single submitter	research	CSER _CC_NCGL, University of Washington	Jun 01, 2014	Low GERP score may suggest that this variant may belong in a lower pathogenicity class -
Likely pathogenic, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	Jul 20, 2017	- -

Hypertrophic cardiomyopathy Uncertain:1 Benign:1

Likely benign, criteria provided, single submitter	research	Genetics and Genomics Program, Sidra Medicine	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Invitae	Jan 28, 2024	This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1459 of the MYH7 protein (p.Lys1459Asn). This variant is present in population databases (rs201307101, gnomAD 0.05%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 17125710, 19150014, 21127202, 22765922, 23794396, 24793961, 28356264, 30871747, 33297573). ClinVar contains an entry for this variant (Variation ID: 43012). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Wolff-Parkinson-White pattern Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Jul 14, 2017

This variant was identified in an individual with Wolff-Parkinson-White syndrome -

Myosin storage myopathy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 20, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Congenital myopathy with fiber type disproportion Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

May 16, 2019

This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP2,PP3,BP6. -

MYH7-related skeletal myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 20, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Congenital myopathy with fiber type disproportion;C1834481:Dilated cardiomyopathy 1S;C1842160:Myosin storage myopathy;C1850709:Myopathy, myosin storage, autosomal recessive;C3495498:Hypertrophic cardiomyopathy 1;C4552004:MYH7-related skeletal myopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 23, 2021

- -

Cardiovascular phenotype Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2020

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
CardioboostCm	Uncertain	0.46
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.18
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.88	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Pathogenic	3.9	H
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.4	D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.064	T
Polyphen		1.0	D
Vest4		0.90
MutPred		0.63		Loss of ubiquitination at K1459 (P = 0.0056);
MVP		0.93
MPC		1.7
ClinPred		0.31	T
GERP RS		1.3
Varity_R		0.51
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201307101; hg19: chr14-23886504;