14-23415651-C-T

Position:

• chr14-23415651-C-T

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PP1_Strong PM2 PS4

This summary comes from the ClinGen Evidence Repository: The NM_000257.4(MYH7):c.5135G>A (p.Arg1712Gln) variant has been reported in >30 individuals with HCM (PS4; Miller 2013 PMID:23054336; Mook 2013 PMID:23785128; Glotov 2015 PMID:25892673; Lopes 2015 PMID:25351510; Helms 2016 PMID:27688314; Mademont-Soler 2017 PMID:28771489; Weissler-Snir 2017 PMID:28193612; van Velzen 2017 PMID:2879411; van Lint 2019 PMID:30847666; Tran Vu 2019 PMID:31308319; Ambry pers. comm.; CHEO pers. comm.; GeneDx pers. comm.; LMM pers. comm.; Mayo pers. comm.; OMGL pers. comm.). This variant segregated with disease in >15 affected relatives with HCM in at least 9 families (PP1_strong; GeneDx pers. comm.; LMM pers. comm.; OMGL pers. comm.). This variant has also been identified in 0.002% (FAF 95% CI; 6/128842) of European chromosomes by gnomAD v2.1.1 (PM2; https://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, this variant meets criteria to be classified as pathogenic for hypertrophic cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): PS4, PP1_strong, PM2. LINK:https://erepo.genome.network/evrepo/ui/classification/CA015727/MONDO:0005045/002

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: MYH7 NM_000257.4 missense
• Clinical Significance: Pathogenic reviewed by expert panel P:30
• Conservation: PhyloP100: 5.66

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]

ENSG00000258444 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PS4: For more information check the summary or visit ClinGen Evidence Repository.
• PM2: For more information check the summary or visit ClinGen Evidence Repository.
• PP1: For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH7	NM_000257.4	c.5135G>A	p.Arg1712Gln	missense_variant	35/40	ENST00000355349.4	NP_000248.2
MYH7	NM_001407004.1	c.5135G>A	p.Arg1712Gln	missense_variant	34/39		NP_001393933.1
MHRT	NR_126491.1	n.83C>T		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH7	ENST00000355349.4	c.5135G>A	p.Arg1712Gln	missense_variant	35/40	1	NM_000257.4	ENSP00000347507.3
ENSG00000258444	ENST00000557368.1	n.172C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152248 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 250956 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135650

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461548 Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9 AN XY: 727074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74380

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000344 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:30

Revision: reviewed by expert panel

Submissions by phenotype

not provided Pathogenic:10

Likely pathogenic, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Clinical Genetics Laboratory, Skane University Hospital Lund	May 27, 2022	- -
Likely pathogenic, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely pathogenic, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Pathogenic, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	MYH7: PP1:Strong, PM5, PS4:Moderate, PP2, PP3 -
Pathogenic, criteria provided, single submitter	clinical testing	GeneDx	Apr 06, 2023	Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30531895, 34542152, 21310275, 21511876, 15483641, 18403758, 25351510, 23074333, 23785128, 24510615, 24835277, 23054336, 27247418, 27688314, 27532257, 28193612, 28241245, 20298698, 29661763, 30022097, 31737537, 30847666, 31447099, 28771489, 29300372, 32894683, 33087929, 34352619, 33673806, 35626289, 35653365) -
Likely pathogenic, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Mar 30, 2023	- -
Likely pathogenic, no assertion criteria provided	clinical testing	Stanford Center for Inherited Cardiovascular Disease, Stanford University	Jan 24, 2014	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. p.Arg1712Gln (c.5135G>A) in the MYH7 gene. Given the data reviewed below, we consider it likely disease causing. This variant has been observed previously in at least 9 unrelated cases of HCM (not including this patient), with weak segregation. Per the ClinVar database, this variant has been observed in 17 individuals from 9 unrelated families (as of June 23, 2015). In 2005 Peng et al submitted the variant to the Harvard Cardiogenomics Sarcomere Mutation Database. Unfortunately no clinical or family data is provided online. GeneDx reports that the variant has been seen in three unrelated cases of HCM and in each case there was another affected first degree relative that also had the variant. This variant is currently present in dbSNP (rs193922390) from a single SNV submission by Corralagen, where they comment “HCM” (thus presumably, this represents another individual with HCM identified with this variant). This missense variant results in a non-conservative amino acid change with a positively charged hydrophilic Arginine replaced with a neutral, hydrophilic Glutamine. Arginine is highly conserved at this residue across several species. A different amino acid change at the same codon has been reported in two different Dutch families with HCM (p.Arg1712Trp) (Hougs et al 2005). This variant falls within the myosin tail domain (which spans residues 1068-1926)." We looked at the paper Mook et al. 2013, but the authors provide little detail about the variant not segregating with disease. In Table 4, they state that this variant was identified with a 70 yo with HCM, and in the notes section they state that it was seen in "9 Dutch index cases (one family no co-segregation in affected daughter)". We emailed the authors in Feb 2015 and have never heard back. In total the variant has not been seen in ~60,800 individuals from the general population. GeneDx notes that p.Arg1712Gln was not reported in 200 presumably healthy controls at of both Caucasian and African American ancestry. There is no variation at codon 1712 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6,300 Caucasian and African American individuals (as of June 23, 2015). This variant is present in 1 individual in the ExAC database which contains exome data from 60,683 individuals of various ancestries (this 1 indiivdual is of European descent). -
Pathogenic, criteria provided, single submitter	clinical testing	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	Oct 23, 2020	- -

Hypertrophic cardiomyopathy Pathogenic:6

Pathogenic, reviewed by expert panel	curation	ClinGen Cardiomyopathy Variant Curation Expert Panel	Dec 09, 2021	The NM_000257.4(MYH7):c.5135G>A (p.Arg1712Gln) variant has been reported in >30 individuals with HCM (PS4; Miller 2013 PMID: 23054336; Mook 2013 PMID: 23785128; Glotov 2015 PMID: 25892673; Lopes 2015 PMID: 25351510; Helms 2016 PMID: 27688314; Mademont-Soler 2017 PMID: 28771489; Weissler-Snir 2017 PMID: 28193612; van Velzen 2017 PMID: 2879411; van Lint 2019 PMID: 30847666; Tran Vu 2019 PMID: 31308319; Ambry pers. comm.; CHEO pers. comm.; GeneDx pers. comm.; LMM pers. comm.; Mayo pers. comm.; OMGL pers. comm.). This variant segregated with disease in >15 affected relatives with HCM in at least 9 families (PP1_strong; GeneDx pers. comm.; LMM pers. comm.; OMGL pers. comm.). This variant has also been identified in 0.002% (FAF 95% CI; 6/128842) of European chromosomes by gnomAD v2.1.1 (PM2; https://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, this variant meets criteria to be classified as pathogenic for hypertrophic cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): PS4, PP1_strong, PM2. -
Likely pathogenic, no assertion criteria provided	clinical testing	Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	Nov 29, 2016	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Centre for Mendelian Genomics, University Medical Centre Ljubljana	Jan 01, 2017	- -
Pathogenic, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Dec 19, 2022	The p.Arg1712Gln variant in MYH7 has been reported in more than 15 individuals with hypertrophic cardiomyopathy (HCM; Morita 2008 PMID: 18403758, Gruner 2011 PMID: 21511876, Mook 2013 PMID: 23785128, Walsh 2016 PMID: 27532257, LMM data), including at least 1 individual with a likely disease-causing variant in another gene. This variant did not segregate with disease in one affected family member from one family (Mook 2013 PMID: 23785128), but did segregate in more than 15 affected individuals with HCM in at least 9 families (LMM internal data, GeneDx personal communication, Mayo Personal Communication, OMGL personal communication). This variant has been identified in 0.0045 (3/68048) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org, v.3.1.2). This variant has been classified as pathogenic on December 9, 2021 by the ClinGen Cardiomyopathy Variant Curation Expert Panel (Variation ID 36642). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HCM. Criteria applied (Richards 2015): PS4, PP1_Strong, PM2_Supporting. -
Pathogenic, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 25, 2023	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1712 of the MYH7 protein (p.Arg1712Gln). This variant is present in population databases (rs193922390, gnomAD 0.005%). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 18403758, 21511876, 23785128, 24510615, 27247418, 27532257, 31308319, 32894683). ClinVar contains an entry for this variant (Variation ID: 36642). 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%. This variant disrupts the p.Arg1712 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15483641). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	All of Us Research Program, National Institutes of Health	Sep 28, 2024	This missense variant replaces arginine with glutamine at codon 1712 in the LMM domain of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over 30 individuals affected with hypertrophic cardiomyopathy (PMID: 18403758, 21511876, 23785128, 24510615, 27247418, 27532257, 28771489, 30297972, 31308319, 33495596, 33495597, 34352619, 34542152, 35026164, 35176171). It has been shown that this variant segregates with disease in over 20 affected relatives across at least 10 families (PMID: 37488328; ClinVar SCV000564455.5). This variant has been shown to have both age- and sex-dependent penetrance (PMID: 37488328). This variant has been identified in 6/282354 chromosomes in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, p.Arg1712Trp, is considered to be disease-causing (Clinvar variation ID: 14118), indicating that arginine at this position is important for MYH7 protein function. Based on the available evidence, this variant is classified as Pathogenic. -

Hypertrophic cardiomyopathy 1 Pathogenic:6

Likely pathogenic, criteria provided, single submitter	clinical testing	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	Jan 13, 2020	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Institute of Human Genetics, University of Leipzig Medical Center	Oct 10, 2022	_x000D_ Criteria applied: PS4_MOD, PM5, PM2_SUP, PP3 -
Pathogenic, no assertion criteria provided	clinical testing	Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	Oct 09, 2023	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	MGZ Medical Genetics Center	Aug 02, 2021	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	Oct 12, 2018	The rare missense variant, c.5135G>A (p.Arg1712Gln) , in the MYH7 gene (seen 6 times in gnomAD) has been observed in at least 10 unrelated probands with hypertrophic cardiomyopathy with evidence of segregation with disease in some families (PMID 18403758, 21511876, 29300372, 23074333, 23785128, 24510615, 27247418). Based upon the above evidence, this c.5135G>A (p.Arg1712Gln) variant in MYH7 is classified as likely pathogenic. -
Likely pathogenic, criteria provided, single submitter	clinical testing	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	May 26, 2020	Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 4-LIKELY PATHOGENIC. 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). (N) 0108 - This gene is known to be associated with both recessive and dominant disease (OMIM). (N) 0112 - Variants in this gene are known to have reduced penetrance (PMID: 29300372). (N) 0200 - Variant is predicted to result in a missense amino acid change from an arginine to a glutamine (exon 35). (N) 0251 - Variant is heterozygous. (N) 0302 - Variant is present in gnomAD <0.001 for a dominant condition (6 heterozygotes, 0 homozygotes). (P) 0502 - Missense variant with conflicting in silico predictions and/or uninformative conservation. (N) 0600 - Variant is located in an annotated domain or motif (Myosin tail; PDB). (N) 0704 - Comparable variant has low previous evidence for pathogenicity. A comparable missense variant resulting in a major amino acid change to a tryptophan, has been previously reported in HCM patients (ClinVar, PMID: 15483641). (N) 0801 - Strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in multiple HCM patients (ClinVar, VCGS, PMID: 29300372, 24510615, 23785128). (P) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign -

Primary familial hypertrophic cardiomyopathy Pathogenic:3

Likely pathogenic, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	May 19, 2017	- -
Pathogenic, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Sep 07, 2023	Variant summary: MYH7 c.5135G>A (p.Arg1712Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251880 control chromosomes. c.5135G>A has been reported in the literature in multiple individuals affected with Hypertrophic Cardiomyopathy (e.g. Lopes_2015, Miller_2013, Morita_2008, Helms_2016, Sepp_2022, Pollman_2021). Additionally, another change at the same amino acid c.5134C>T (p.Arg1712Trp) has been classified as pathogenic/likely pathogenic in ClinVar by multiple submitters supporting the functional importance of this residue of the protein. These data indicate that the variant is very likely to be associated with disease. One publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect. The following publications have been ascertained in the context of this evaluation (PMID: 18403758, 20298698, 23074333, 24835277, 27247418, 27532257, 27688314, 28193612, 25892673, 21511876, 33673806, 24510615, 25351510, 23054336, 23785128, 35626289, 34830538). 21 submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. -
Likely pathogenic, criteria provided, single submitter	clinical testing	Blueprint Genetics	Nov 04, 2015	- -

Cardiomyopathy Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Oct 18, 2023	This missense variant replaces arginine with glutamine at codon 1712 in the LMM domain of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over 30 individuals affected with hypertrophic cardiomyopathy (PMID: 18403758, 21511876, 23785128, 24510615, 27247418, 27532257, 28771489, 30297972, 31308319, 33495596, 33495597, 34352619, 34542152, 35026164, 35176171). It has been shown that this variant segregates with disease in over 20 affected relatives across at least 10 families (PMID: 37488328; ClinVar SCV000564455.5). This variant has been shown to have both age- and sex-dependent penetrance (PMID: 37488328). This variant has been identified in 6/282354 chromosomes in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, p.Arg1712Trp, is considered to be disease-causing (Clinvar variation ID: 14118), indicating that arginine at this position is important for MYH7 protein function. Based on the available evidence, this variant is classified as Pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	Apr 27, 2023	- -

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 Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 06, 2021

- -

Cardiovascular phenotype Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2023

The p.R1712Q pathogenic mutation (also known as c.5135G>A), located in coding exon 33 of the MYH7 gene, results from a G to A substitution at nucleotide position 5135. The arginine at codon 1712 is replaced by glutamine, an amino acid with highly similar properties. This variant has been reported in multiple individuals with hypertrophic cardiomyopathy (HCM) (Morita H et al. N. Engl. J. Med. 2008; 358:1899-908; Gruner C et al. Circ Cardiovasc Genet 2011;4:288-95; Mook OR et al. J. Med. Genet., 2013;50:614-26; Tran Vu MT et al. Circ. J., 2019 Aug;83:1908-1916). One of those individuals also harbored an alteration in another sarcomere protein gene, but no information was provided about the alterations in other affected relatives in the family (Gruner C et al. Circ Cardiovasc Genet 2011;4:288-95). This variant was reported not to segregate with disease in a family in the literature (Mook OR et al. J. Med. Genet., 2013;50:614-26), and at least two clinical laboratories have observed segregation of this variant with HCM in multiple families (personal communications). In addition, this alteration has been described in HCM cohorts, although clinical details were limited (Kapplinger JD et al. J Cardiovasc Transl Res. 2014;7(3):347-61; Lopes LR et al. Heart. 2015;101(4):294-301; Walsh R et al. Genet. Med. 2017;19:192-203). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. -

Asymmetric septal hypertrophy Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

NIHR Bioresource Rare Diseases, University of Cambridge

Jan 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
CardioboostCm	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.82	D
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.75	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Uncertain	2.5	M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.011	D
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.58		Gain of catalytic residue at L1715 (P = 0.0449);
MVP		0.94
MPC		1.3
ClinPred		0.93	D
GERP RS		5.4
Varity_R		0.62
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs193922390; hg19: chr14-23884860;