NM_000257.4:c.958G>A

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong

The NM_000257.4(MYH7):c.958G>A(p.Val320Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,992 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 pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V320E) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MYH7
NM_000257.4 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:13U:1

Conservation

PhyloP100: 7.77

Publications

16 publications found

Variant links:

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

MYH7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 19 ACMG points.

PM1

In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 24 uncertain in NM_000257.4

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr14-23430600-A-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 619261.Status of the report is criteria_provided_single_submitter, 1 stars.

PP2

Missense variant in the MYH7 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 341 curated pathogenic missense variants (we use a threshold of 10). The gene has 16 curated benign missense variants. Gene score misZ: 3.9329 (above the threshold of 3.09). Trascript score misZ: 6.7889 (above the threshold of 3.09). GenCC associations: The gene is linked to myopathy, myosin storage, autosomal recessive, MYH7-related skeletal myopathy, congenital myopathy 7A, myosin storage, autosomal dominant, Ebstein anomaly, hyaline body myopathy, left ventricular noncompaction, hypertrophic cardiomyopathy 1, dilated cardiomyopathy 1S, dilated cardiomyopathy, congenital heart disease, familial isolated dilated cardiomyopathy, myopathy, myosin storage, autosomal dominant, arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.963

PP5

Variant 14-23430601-C-T is Pathogenic according to our data. Variant chr14-23430601-C-T is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 161328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH7	NM_000257.4 link	c.958G>A	p.Val320Met	missense_variant	Exon 11 of 40	ENST00000355349.4	NP_000248.2	P12883
MYH7	NM_001407004.1 link	c.958G>A	p.Val320Met	missense_variant	Exon 10 of 39		NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH7	ENST00000355349.4 link	c.958G>A	p.Val320Met	missense_variant	Exon 11 of 40	1	NM_000257.4	ENSP00000347507.3	P12883
MYH7	ENST00000713768.1 link	c.958G>A	p.Val320Met	missense_variant	Exon 11 of 41			ENSP00000519070.1
MYH7	ENST00000713769.1 link	c.958G>A	p.Val320Met	missense_variant	Exon 10 of 39			ENSP00000519071.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251342

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111970

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00000944

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:13Uncertain:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Pathogenic:3

Aug 06, 2012

Stanford Center for Inherited Cardiovascular Disease, Stanford University

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

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.Val320Met (c.958 G>A) in the MYH7 gene. We re-reviewed these results on 6/27/2012 and again on 10/1/13 and February 9th, 2015. Based on the strong case data and very low frequency in the general population, we consider this variant likely disease causing. The variant has been seen in at least 10 unrelated cases of HCM (not including this patient). There is weak segregation data. Havndrup et al (2003) observed this variant in a Danish woman with HCM (likely the same case that was included in Ho et al 2009). Her 15yo daughter had a proximal 'septal bulb' and also carried the variant. Fokstuen et al (2011) observed the variant in one patient with HCM recruited from Europe (not Denmark). Santos et al (2012) reported the variant in one patient with HCM in their Portugese cohort. We have seen this variant in one other HCM patient in our cohort. She had 12 HCM genes sequenced at PGxHealth/Familion and only this variant was found. Marsiglia et al (2013) sequenced MYH7, MYBPC3, TNNT2 in 268 Brazilian patients with HCM and found the variant in 5 patients. Alvarez-Acosta et al (2014) reported the variant in 1 of 124 HCM patients recruited from a clinic in Spain. It isn't entirely clear but it looks like the patient underwent sequencing of MYH7, MYBPC3, TNNT2, TNNI3, TPM1, ACTC, MYL2, MYL3, TNNC1. The patient also had a variant in MYL2. He had a relatively severe phenotyped, diagnosed at 16yo, with atrial fibrillation, 2.6 cm wall thickness, syncope, left ventricular outflow tract obstruction, heart failure, LBBB, ICD, and underwent alcohol ablation. His first cousin carried only the MYL2 variant and also had HCM. In silico analysis with PolyPhen-2 predicts the variant to be probably damaging. The valine at codon 320 is completely conserved across species, though not all neighboring amino acids are. I could not find any other variants reported in association with disease at this codon, though there are a few at nearby codons (p.Phe312Cys, p.Ala326Pro). In total the variant has been seen in ~1-4/60,452 published controls, laboratory controls, and publicly available population datasets. The variant was reported online in 2 of 4300 Caucasian individuals and 0 of 2203 African-American individuals in the NHLBI Exome Sequencing Project dataset (as of 10/1/13). The phenotype of those individuals is not publicly available, however the cohorts that were merged to create this dataset were all either general population samples or samples recruited for common cardiovascular disease such as hypertension. Of note, variants with strong evidence for pathogenicity have been observed at similar low frequencies in this data set. The variant was reported online in 1 of 59,906 individuals in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of February 9th, 2015). Specifically, the variant was observed in 1 individual of African descent. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease. Of note, the ESP and ExAC databases overlap (ExAC includes ESP). The discrepancy between them may be attributable to the primary data being re-analyzed in ExAC. The Seidman group observed the variant in 2 of 1963 individuals from the Jackson Heart Study who underwent sequencing of eight sarcomere genes (Bick et al 2012). They note the following about those individuals phenotypes: a 41yo with left ventricular wall thickness of 1 cm, LVDD of 4.2, LAD of 3.83, and FS of 0.38 and no known physiological risk factors; a 63yo -

Jan 17, 2022

Revvity Omics, Revvity

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 13, 2025

GeneDx

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Not observed at 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: 23299917, 24093860, 25637381, 23197161, 22429680, 12566107, 27247418, 27532257, 22857948, 21239446, 33588347, 20031602, 33673806, 34542152, 25937619, 33764162, 29300372, 37652022, 28771489) -

Hypertrophic cardiomyopathy

Pathogenic:3

Dec 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 320 of the MYH7 protein (p.Val320Met). This variant is present in population databases (rs376897125, gnomAD 0.007%). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 12566107, 20031602, 21239446, 22857948, 24093860, 27247418). ClinVar contains an entry for this variant (Variation ID: 161328). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MYH7 protein function with a positive predictive value of 95%. This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). For these reasons, this variant has been classified as Pathogenic. -

Jul 29, 2024

All of Us Research Program, National Institutes of Health

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This missense variant replaces valine with methionine at codon 320 of the MYH7 protein. This variant is found within a highly conserved region of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). 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 at least thirteen unrelated individuals affected with hypertrophic cardiomyopathy (PMID: 12566107, 21239446, 22857948, 24093860, 27532257, 28771489, 30775854, 33588347, 33764162). This variant has been identified in 4/251342 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. -

Feb 06, 2023

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.Val320Met variant in MYH7 has been reported in over 20 individuals with hypertrophic cardiomyopathy (HCM; Brito 2012 PMID: 22857948, Fokstuen 2011 PMID: 21239446, Havndrup 2003 PMID: 12566107, Homburger 2016 PMID: 27247418, Jensen 2013 PMID: 23197161, Marsiglia 2013 PMID: 24093860, Walsh 2017 PMID: 27532257, LMM data) and segregated with disease in at least one affected relative from one family (Havndrup 2003 PMID: 12566107). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID: 161328) and has also been identified in 0.0029% (2/68040) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.1). Computational prediction tools and conservation analysis are consistent with pathogenicity. This variant lies in the head region of the protein and missense variants in this region are statistically more likely to be disease-associated (Walsh 2017 PMID: 27532257). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant HCM. ACMG/AMP criteria applied: PS4, PM2_Supporting, PP3, PM1. -

Hypertrophic cardiomyopathy 1

Pathogenic:3

Jun 11, 2020

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Likely Pathogenic. ClinGen MYH7 guidelines: Likely Pathogenic: PM1 + PM2 + PS4 + PP3 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) For this patient: autosomal dominant inheritance with digenic dominance applies (Cardiomyopathy, hypertrophic, 1. OMIM: 192600) 0112 - Variants in this gene are known to have reduced penetrance: PMID: 29300372: Kelly, MA. et al. (2018), Florescu, C. (2017) (N) 0200 - Variant is predicted to result in a missense amino acid change from valine to methionine (exon 11). (N) 0251 - Variant is heterozygous. (N) 0302 - Variant is present in gnomAD <0.001 for a dominant condition (0.0000159 (4 Het, 0 Hom) gnomAD v2.1.1. (P) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (P) 4/4 in silico analyses. Minor amino acid. High conservation. 0602 - Variant is located in a hotspot region or cluster of pathogenic variants. (P) Hotspot region (amino acids 181-937) (PMID: 29300372). 0708 Comparable variants have conflicting previous evidence for pathogenicity. (N) p.(Val320Glu), major amino acid change: Likely pathogenic in ClinVar x1. LOVD3: 2x Likely pathogenic + 2x VUS by VKGL data sharing initiative. 0801 Strong previous evidence of pathogenicity in unrelated individuals. (P) >15 unrelated probands with this variant. ClinVar: Conflicting interpretations of pathogenicity: 7 submissions: 5x Likely Pathogenic + 2x VUS. Publications: PMID: 12566107 (and follow-up PMID: 23197161). PMID: 21239446. PMID: 22857948. PMID: 24093860. Álvarez-Acosta, L. et al. (2014). PMID: 27247418. PMID: 27532257. 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign -

Laboratory of Genetics and Molecular Cardiology, University of São Paulo

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 10, 2020

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:research

- -

Primary familial hypertrophic cardiomyopathy

Pathogenic:1Uncertain:1

Jun 09, 2014

Blueprint Genetics

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 01, 2014

CSER _CC_NCGL, University of Washington

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

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

Pathogenic:1

Jun 17, 2024

Fulgent Genetics, Fulgent Genetics

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiomyopathy

Pathogenic:1

May 22, 2024

Color Diagnostics, LLC DBA Color Health

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This missense variant replaces valine with methionine at codon 320 of the MYH7 protein. This variant is found within a highly conserved region of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). Computational prediction tools indicate that this variant has a deleterious impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in more than fifteen unrelated individuals affected with hypertrophic cardiomyopathy (PMID: 12566107, 21239446, 22857948, 24093860, 27532257, 28771489, 30775854, 33588347, 33673806, 33764162, 34542152, 38489124). This variant has been identified in 4/251342 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. -

Cardiovascular phenotype

Pathogenic:1

Apr 25, 2025

Ambry Genetics

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.958G>A (p.V320M) alteration is located in exon 11 (coding exon 9) of the MYH7 gene. This alteration results from a G to A substitution at nucleotide position 958, causing the valine (V) at amino acid position 320 to be replaced by a methionine (M). Based on data from gnomAD, the A allele has an overall frequency of 0.002% (4/251342) total alleles studied. The highest observed frequency was 0.006% (1/16250) of African alleles. This variant has been reported in numerous hypertrophic cardiomyopathy cohorts (Havndrup, 2003; Brito, 2012; Jensen, 2013; Marsiglia, 2013). This amino acid position is highly conserved in available vertebrate species. This alteration is located in the myosin head domain, which contains a statistically significant clustering of pathogenic missense variants (Homburger, 2016; Walsh, 2017; Ambry internal data). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

CardioboostCm

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.94

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.95

MetaRNN

Pathogenic

0.96

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.4

PhyloP100

7.8

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.6

REVEL

Pathogenic

0.90

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.94

MVP

0.93

MPC

2.1

ClinPred

0.96

GERP RS

3.4

Varity_R

0.79

gMVP

0.65

Mutation Taster

=4/96

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over