14-23418398-G-T

Variant names:

• chr14-23418398-G-T
• rs141764279
• NM_000257.4:c.3981C>A

Variant summary

Our verdict is Likely benign. The variant received -12 ACMG points: 0P and 12B. BS4 BA1

This summary comes from the ClinGen Evidence Repository: The c.3981C>A (p.Asn1327Lys) variant in MYH7 has been identified in 0.16% (FAF 95% CI; 24/10156) of Ashkenazi Jewish chromosomes in gnomAD v2.1.1 (https://gnomad.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BA1; Kelly 2018 PMID:29300372). Based on criteria selected, this variant should be classified as benign; however, the expert panel felt that since frequency in other populations is not as elevated as in the Ashkenazi Jewish population, it warrants adjusting in the final classification to likely benign. Therefore, this variant is classified as likely benign for cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): BA1 with expert panel adjustment. LINK:https://erepo.genome.network/evrepo/ui/classification/CA014310/MONDO:0005045/002

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: MYH7 NM_000257.4 missense
• Clinical Significance: Likely benign reviewed by expert panel U:7 B:15
• Conservation: PhyloP100: -3.31
• Publications: 17 publications found

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]

MYH7 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• dilated cardiomyopathy 1S

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• MYH7-related skeletal myopathy

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• myopathy, myosin storage, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• myopathy, myosin storage, autosomal dominant

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• congenital myopathy 7A, myosin storage, autosomal dominant

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Ebstein anomaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hyaline body myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• left ventricular noncompaction

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -12 ACMG points.

• BS4: For more information check the summary or visit ClinGen Evidence Repository.
• BA1: For more information check the summary or visit ClinGen Evidence Repository.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000257.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7	NM_000257.4	MANE Select	c.3981C>A	p.Asn1327Lys	missense	Exon 30 of 40	NP_000248.2
	MYH7	NM_001407004.1		c.3981C>A	p.Asn1327Lys	missense	Exon 29 of 39	NP_001393933.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7	ENST00000355349.4	TSL:1 MANE Select	c.3981C>A	p.Asn1327Lys	missense	Exon 30 of 40	ENSP00000347507.3
	MYH7	ENST00000713768.1		c.3981C>A	p.Asn1327Lys	missense	Exon 30 of 41	ENSP00000519070.1
	MYH7	ENST00000713769.1		c.3981C>A	p.Asn1327Lys	missense	Exon 29 of 39	ENSP00000519071.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000113 AC: 28 AN: 247224 AF XY: 0.0000971

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00243

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.0000461 AC: 67 AN: 1454010 Hom.: 0 Cov.: 31 AF XY: 0.0000512 AC XY: 37 AN XY: 722036

African (AFR) AF: 0.00 AC: 0 AN: 33302

American (AMR) AF: 0.00 AC: 0 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.00201 AC: 52 AN: 25926

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.00 AC: 0 AN: 86000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00000813 AC: 9 AN: 1106650

Other (OTH) AF: 0.000100 AC: 6 AN: 59990

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152180 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00198 Hom.: 4

Bravo AF: 0.0000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000989 AC: 12

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:7 Benign:15

Revision: reviewed by expert panel

Submissions by phenotype

not provided Benign:4

Sep 30, 2018

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nov 04, 2016

Stanford Center for Inherited Cardiovascular Disease, Stanford University

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: provider interpretation

Given the co-occurrence of another variant in several cases, the failure to segregate, and the apparent presence of the variant at an appreciable frequency in multiple general population samples, including individuals of Ashkenazi Jewish ancestry, (reviewed below) we consider this variant probably benign and do not consider it appropriate for testing family members ("predictive genetic testing"). Note this includes this patient's data. Summary: -Seen in at least 14 presumably unrelated cases of HCM (2 published, 12 unpublished). -In 3 of 6 cases who had sequencing of at least MYH7, MYBPC3, and TNNT2 another variant (VUS or likely pathogenic) was present. - One proband carried a second variant in MYL2 (c.37G>A; p.Ala13Thr) (ClinVar: likely pathogenic by GeneDx (Aug 12, 2014) and a VUS by LMM (Mar 16, 2009)) - 36-year-old female proband with LVWT of 25 mm carried a second variant in MYBPC3 (c.3535G>A; p.Glu1179Lys) (ClinVar: a VUS by LMM (Jul 1, 2014) and CHOE (date of submission not reported), and likely pathogenic by GeneDx (May 21, 2014)) - 18-year-old proband with LVWT of 21 mm carried a second variant in PRKAG2 (c.866T>C; p.Val289Ala) (ClinVar: a VUS by GeneDx (Oct 4, 2012)) -Segregation data: LMM reports that in two families the variant failed to segregate with disease in another affected family member. A reported case is suspicious for failure to segregate (Houghs et al) -The variant is too common in Ashkenazi Jewish reference samples (ex. 19 of 4,800 individuals in gnomAD). Published cases: Hougs et al. (2005) and Jensen et al. (2013) reported this variant in 1 out of 92 European patients with HCM that were cared for in Copenhagen University Hospital in Copenhagen, Denmark, who underwent analysis of the MYH7, MYBPC3, TPM1, TNNT2, TNNI3, ACTC, MYL2, and MYL3 genes. The proband is a 46-year-old male with LVWT of 20 mm, who needed percutaneous transluminal septal myocardial ablation for treatment. This proband carried an additional variant in MYL2 gene (c.37G>A; p.Ala13Thr), which is classified as likely pathogenic by GeneDx (Aug 12, 2014) and a VUS by LMM (Mar 16, 2009) per ClinVar. He had a 49-year-old affected brother with LVWT of 14 mm, who carried the MYH7 variant, and was obese and hypertensive and thus may have had secondary hypertrophy and not HCM. His affected fraternal twin sister, who had LVWT of 23 mm, carried the MYL2 mutation, but did not carry the MYH7 variant; his deceased mother was affected, and was an obligate carrier for both of the variants; his 10-year-old unaffected son also carried both for the variants. No additional phenotypic information or variants were provided by the authors. Miller et al. (2012) reported this variant in 1 out of 46 patients with HCM that were cared for in Cincinnati Children's Hospital Medical Center in Cincinnati, OH, who underwent analysis of MYH7, TNNT2, TPM1, MYBPC2, TNNI3, MYL2, MYL3, ACTC, TTR, TNNC1, CAV3, LAMP2, GLA, PRKAG2, MTTC, MTTI, MTTK, LMNA, ZAS/LDB3, DES, SGCD, PLN, ACTC1, TNNI2, TAZ, TTR, MTTL1, MTTQ, MTTH, MTTS1, MTTS2, MTND1, MTND5, and MTND6 genes. Ancestry of the patient was not reported. The study cohort included ~79% non-Hispanic Caucasian, 12 % Black, <2 % Asian, and 7 % Hispanic patients. No additional phenotypic information or variants were provided by the authors. Xu et al. (2015) used whole exome sequencing (WES) to query the genetic cause of patients with "sporadic" HCM. Study was conducted on 74 Han Chinese patients with HCM who did not have mutations in the 8 sarcomere genes: MYH7, MYBPC3, TNNT2, TNNI3, TPM1, ACTC1, MYL2 and MYL3. The genes that were included are not as established in their cause of HCM: RYR2,CALM3, JPH2, PLN, SRI, CALR3 and CASQ2,AGK, COX15, GLA, FXN, PRKAG2, MRPL3, LAMP2, TAZ and SLC25A4. 94% of the targeted regions were covered at least 4x. The authors analyzed novel or rare variants in known HCM genes. Mutations in MYH7 were found in 2 patients even though they should have been filtered out. N1327K (p.Asn13

Oct 02, 2024

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria.

Aug 14, 2017

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.Asn1327Lys variant (rs141764279) has been previously reported to segregate with disease in a family with hypertrophic cardiomyopathy (Hougs 2005 and Jensen 2013); however, three out of four of the affected individuals also carried a variant in MYL2. In addition, this variant has been identified in cohorts of unrelated, presumably healthy individuals (Ng 2013 and Kapplinger 2014). This variant is listed in the Genome Aggregation Database (gnomAD) browser with a frequency of 0.2% in Ashkenazi Jewish individuals (identified in 20 out of 9950 chromosomes), which is higher than expected for a pathogenic variant in MYH7. It is listed in the ClinVar database (Variation ID: 36641) as likely benign according to multiple labs, including a ClinGen expert panel. Functional data demonstrated that the p.Asn1327Lys mutant MYH7 protein expressed in adult rat cardiomyocytes had reduced incorporation into sarcomeres; however, the mutant protein did not alter contractile properties, raising questions about the physiological relevance of this reduced incorporation (Wolny 2014). Based on these observations, the p.Asn1327Lys variant is classified as likely benign.

Primary familial hypertrophic cardiomyopathy Uncertain:3

Jun 24, 2013

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

May 04, 2024

Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Heterozygous variant NM_000257.4:c.3981C>A (p.Asn1327Lys) in the MYH7 gene was found on WES data in male proband (26 y.o., Caucasian) with un obstructive hypertrophic cardiomyopathy, who underwent a myoectomy. Additional candidate heterozygous variant NM_000256.3:c.1505G>A (p.Arg502Gln) (Class V of pathogenicity) in the MYBPC3 gene was found in this proband. Clinvar contains 20 entries for this variant. The variant is described in the literature in 3 patients with hypertrophic cardiomyopathy and in 12 unpublished patients (PS4_supporting). NM_000257.4:c.3981C>A (p.Asn1327Lys) is in the Genome Aggregation Database (gnomAD) v4.1.0 with total MAF=0.00005105 (Date of access 04-05-2024). A functional study supports the effect of this variant on protein (PM1): PMID: 24047955. Most in silico predictors are inconclusive in the results (varsome.com). In accordance with ACMG (2015) criteria this variant is classified as Variant of Uncertain Significance (VUS) with following criteria selected: PS4_supporting, PM1.

Jun 01, 2014

CSER _CC_NCGL, University of Washington

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

Low GERP score may suggest that this variant may belong in a lower pathogenicity class

Cardiomyopathy Benign:3

Feb 05, 2024

All of Us Research Program, National Institutes of Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Dec 28, 2017

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 18, 2018

Color Diagnostics, LLC DBA Color Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Cardiovascular phenotype Uncertain:1 Benign:1

Mar 09, 2019

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:2

Jul 09, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: MYH7 c.3981C>A (p.Asn1327Lys) results in a non-conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function all suggest that this variant is likely to be disruptive. The variant allele was found at a frequency of 5.1e-05 in 1540170 control chromosomes, predominantly at a frequency of 0.002 within the Ashkenazi Jewish subpopulation in the gnomAD database. The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYH7 causing Hypertrophic Cardiomyopathy phenotype (0.001). c.3981C>A has been observed in individual(s) affected with Hypertrophic Cardiomyopathy as well as healthy controls (e.g. Houghs_2005, Kapplinger_2014, Ng_2013, Park_2022, Miller_2012, Jensen_2013, Xu_2015). One publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Wolny_2013). The following publications have been ascertained in the context of this evaluation (PMID: 15483641, 23197161, 24510615, 23054336, 23861362, 34542152, 24047955, 26573135). ClinVar contains an entry for this variant (Variation ID: 36641). Based on the evidence outlined above, the variant was classified as likely benign.

Oct 08, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Asn1327Lys in exon 30 of MYH7: This variant has been reported in 1 individual with HCM who carried a second variant of unknown significance, but did not segre gate with disease in 1 affected relative (Houghs 2005, Jensen 2013). It has also been identified by our laboratory in 9 individuals with HCM, but did not segreg ate with disease in 2 individuals from 2 families (LMM unpublished data). In vit ro functional studies provide some evidence that this variant may impact protein function (Wolny 2013). However, in vitro assays may not accurately represent bi ological function. While this variant is rare in the general population (1/8598 European American chromosomes in the NHLBI Exome Sequencing Project, http://evs. gs.washington.edu/EVS/; rs141764279), it appears to be common amongst Ashkenazi Jewish individuals with a prevalence that greatly exceeds that of HCM (5/282 chr omosomes, 1.8%; LMM unpublished data). In summary, the frequency of this variant in the Ashkenazi Jewish population and multiple occurrences of non-segregation with disease indicate this variant is likely benign, although a modifying effect cannot be ruled out.

Hypertrophic cardiomyopathy Benign:2

Apr 24, 2020

ClinGen Cardiomyopathy Variant Curation Expert Panel

Significance: Likely benign

Review Status: reviewed by expert panel

Collection Method: curation

The c.3981C>A (p.Asn1327Lys) variant in MYH7 has been identified in 0.16% (FAF 95% CI; 24/10156) of Ashkenazi Jewish chromosomes in gnomAD v2.1.1 (https://gnomad.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BA1; Kelly 2018 PMID:29300372). Based on criteria selected, this variant should be classified as benign; however, the expert panel felt that since frequency in other populations is not as elevated as in the Ashkenazi Jewish population, it warrants adjusting in the final classification to likely benign. Therefore, this variant is classified as likely benign for cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): BA1 with expert panel adjustment.

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Myosin storage myopathy Uncertain:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;C1834481:Dilated cardiomyopathy 1S;C1842160:Myosin storage myopathy;C1850709:Myopathy, myosin storage, autosomal recessive;C3495498:Hypertrophic cardiomyopathy 1;C4552004:MYH7-related skeletal myopathy Uncertain:1

Oct 31, 2018

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Hypertrophic cardiomyopathy 1 Uncertain:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

MYH7-related skeletal myopathy Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Ventricular fibrillation Benign:1

Oct 02, 2018

Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MYH7-related disorder Benign:1

May 10, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
CardioboostCm	Uncertain	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.81	D
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.75	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		-3.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.91	T
Polyphen		0.53	P
Vest4		0.92
MutPred		0.58		Gain of ubiquitination at N1327 (P = 0.0267)
MVP		0.94
MPC		0.97
ClinPred		0.26	T
GERP RS		-0.39
Varity_R		0.25
gMVP		0.81
Mutation Taster		=6/94	disease causing

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

Other links and lift over

dbSNP: rs141764279; hg19: chr14-23887607;