ClinVar Genomic variation as it relates to human health
NM_000257.4(MYH7):c.2717A>G (p.Asp906Gly)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000257.4(MYH7):c.2717A>G (p.Asp906Gly)
Variation ID: 14125 Accession: VCV000014125.40
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 14q11.2 14: 23424112 (GRCh38) [ NCBI UCSC ] 14: 23893321 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 29, 2016 Apr 20, 2024 Dec 15, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000257.4:c.2717A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000248.2:p.Asp906Gly missense NC_000014.9:g.23424112T>C NC_000014.8:g.23893321T>C NG_007884.1:g.16550A>G LRG_384:g.16550A>G LRG_384t1:c.2717A>G P12883:p.Asp906Gly - Protein change
- D906G
- Other names
- NM_000257.3(MYH7):c.2717A>G
- Canonical SPDI
- NC_000014.9:23424111:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MYH7 | No evidence available | No evidence available |
GRCh38 GRCh37 |
3578 | 4827 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (2) |
criteria provided, single submitter
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Aug 22, 2019 | RCV000015185.28 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 21, 2021 | RCV000035817.7 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Sep 21, 2022 | RCV000158569.21 | |
Pathogenic (3) |
reviewed by expert panel
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Dec 15, 2016 | RCV000469895.15 | |
Pathogenic (1) |
criteria provided, single submitter
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May 2, 2022 | RCV000617405.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 28, 2021 | RCV000762923.3 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Apr 28, 2023 | RCV001181317.6 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Dec 15, 2016)
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reviewed by expert panel
Method: curation
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Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Cardiomyopathy Variant Curation Expert Panel
Accession: SCV000564437.5
First in ClinVar: Feb 26, 2016 Last updated: Dec 11, 2022 |
Comment:
The c.2717A>G (p.Asp906Gly) variant in MYH7 has been reported in >20 individuals with hypertrophic cardiomyopathy (PS4; PMID:27532257; PMID:12081993; PMID:15528230; PMID:16267253; PMID:24510615; Partners LMM ClinVar SCV000059468.5). … (more)
The c.2717A>G (p.Asp906Gly) variant in MYH7 has been reported in >20 individuals with hypertrophic cardiomyopathy (PS4; PMID:27532257; PMID:12081993; PMID:15528230; PMID:16267253; PMID:24510615; Partners LMM ClinVar SCV000059468.5). This variant segregated with disease in 10 affected individuals (PP1_Strong; PMID:12081993; PMID:15528230). This variant was absent from large population studies (PM2; http://exac.broadinstitute.org). This variant lies in the head region of the protein (aa 181-937) and missense variants in this region are statistically more likely to be disease-associated (PM1; PMID:27532257). 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; PM1; PM2 (less)
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Pathogenic
(Nov 10, 2015)
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criteria provided, single submitter
Method: clinical testing
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Primary familial hypertrophic cardiomyopathy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV000264085.2
First in ClinVar: Feb 26, 2016 Last updated: Mar 04, 2019 |
Number of individuals with the variant: 1
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Pathogenic
(May 25, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000861540.1
First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Nov 21, 2021)
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criteria provided, single submitter
Method: clinical testing
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Primary familial hypertrophic cardiomyopathy
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000917840.2
First in ClinVar: Jun 03, 2019 Last updated: Dec 25, 2021 |
Comment:
Variant summary: MYH7 c.2717A>G (p.Asp906Gly) results in a non-conservative amino acid change located in the Myosin tail domain (IPR002928) of the encoded protein sequence. Three … (more)
Variant summary: MYH7 c.2717A>G (p.Asp906Gly) results in a non-conservative amino acid change located in the Myosin tail domain (IPR002928) of 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 4e-06 in 252714 control chromosomes. c.2717A>G, has been reported in the literature in to co-segregate with disease multiple individuals affected with Hypertrophic Cardiomyopathy (including apical hypertrophy) but also in unaffected individuals and is considered to have reduced penetrance (example, Ho_2002, Arad_2005, Alpert_2005, Miller_2012, Kapplinger_2014). This variant was also reported in compound heterozygosity with MYBPC3 c.3226_3227insT (p.Asp1076fsX6) and MYH7 c.2722C>G (p.Leu908Val) (Alpert_MYH7_AJPHCP_2005 and internal specimen). Compound heterozygotes (2 variants in MYH7, 2 variants in MYBPC3, or 1 variant each in MYH7 and MYBPC3) are known to be associated with more severe prognosis (example, Alpert_2005). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function where it increased velocity of actin translocation compared to wild-type (example, Alpert_2005). Multiple clinical diagnostic laboratories and an expert panel (ClinGen Cardiomyopathy Variant Curation Expert Panel) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(May 02, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000736390.4
First in ClinVar: Apr 14, 2018 Last updated: Nov 29, 2022 |
Comment:
The p.D906G pathogenic mutation (also known as c.2717A>G), located in coding exon 21 of the MYH7 gene, results from an A to G substitution at … (more)
The p.D906G pathogenic mutation (also known as c.2717A>G), located in coding exon 21 of the MYH7 gene, results from an A to G substitution at nucleotide position 2717. The aspartic acid at codon 906 is replaced by glycine, an amino acid with similar properties. This alteration is located in the myosin head domain, which contains a statistically significant clustering of pathogenic missense variants (Homburger JR et al. Proc Natl Acad Sci U S A, 2016 06;113:6701-6; Walsh R et al. Genet Med, 2017 02;19:192-203; Ambry internal data). This alteration has been identified in a number of hypertrophic cardiomyopathy (HCM) cohorts and is reported to co-segregate with disease in two families, although a second segregating MYH7 alteration was noted in one family (Ho CY et al. Circulation. 2002;105:2992-7; Alpert NR et al. Am. J. Physiol. Heart Circ. Physiol. 2005;288:H1097-102; Arad M et al. Circulation. 2005;112:2805-11; Miller EM et al. J Genet Couns. 2013;22:258-67; Kapplinger JD et al. J Cardiovasc Transl Res. 2014;7:347-61; Lopes LR et al. Heart. 2015;101:294-301; Walsh R et al. Genet. Med. 2017;19:192-203; Weissler-Snir A et al. Circ Cardiovasc Imaging. 2017;10:e005311). One in vitro functional assay using isolated myosin from p.D906G carriers found increased velocity of actin translocation compared to wild-type, and a second functional assay suggested that the p.D906G mutation weakens an interaction between the S1 and S2 domains of MYH7 that sequesters myosin heads and prevents them from interacting with actin (Alpert NR et al. Am. J. Physiol. Heart Circ. Physiol. 2005;288:H1097-102; Nag S et al. Nat. Struct. Mol. Biol. 2017;24:525-533). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Sep 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000208504.10
First in ClinVar: Feb 24, 2015 Last updated: Mar 04, 2023 |
Comment:
Not observed at a significant frequency in large population cohorts (gnomAD); A functional study demonstrated that this missense variant caused myosin to move actin at … (more)
Not observed at a significant frequency in large population cohorts (gnomAD); A functional study demonstrated that this missense variant caused myosin to move actin at an increased velocity compared to control (Alpert et al., 2005); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported as pathogenic in ClinVar by the ClinGen Inherited Cardiomyopathy Expert Panel (SCV000564437.2; ClinVar); This variant is associated with the following publications: (PMID: 28166811, 27532257, 28606303, 24704860, 29300372, 15528230, 28481356, 29203298, 23054336, 12081993, 16267253, 24510615, 26914223, 27247418, 21310275, 28193612, 28241245, 31006259, 32894683, 33087929) (less)
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Pathogenic
(Jun 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV003838754.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Pathogenic
(Sep 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001715068.2
First in ClinVar: Jun 15, 2021 Last updated: Jan 26, 2024 |
Comment:
PP1_strong, PP3, PM1, PM2, PS4
Number of individuals with the variant: 2
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Pathogenic
(Nov 06, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002017667.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Apr 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV001346438.3
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces aspartic acid with glycine at codon 906 of the MYH7 protein. Computational prediction suggests that this variant may have a deleterious … (more)
This missense variant replaces aspartic acid with glycine at codon 906 of the MYH7 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). 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). An in vitro functional motility assay has shown that this variant enhances myosin velocity-generating capacity (PMID: 15528230). Another in-vitro functional study has shown that this variant decreased affinity to the S1 binding domain (PMID: 28481356). This variant has been reported in over 20 individuals affected with hypertrophic cardiomyopathy (PMID: 16267253, 24510615, 24704860, 27532257, 33495597, 35026164). It has been shown that this variant segregates with disease in over 10 affected individuals from multiple families (PMID: 12081993, 15528230). This variant has been identified in 1/251460 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Aug 22, 2019)
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criteria provided, single submitter
Method: research
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Hypertrophic cardiomyopathy 1
Affected status: unknown
Allele origin:
unknown
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HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: AGHI GT
Accession: SCV000993573.2 First in ClinVar: Oct 01, 2019 Last updated: Oct 01, 2019 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
Observation 3:
Number of individuals with the variant: 1
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Pathogenic
(Feb 04, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV002051556.3
First in ClinVar: Jan 08, 2022 Last updated: Feb 11, 2022 |
Comment:
PS4, PM1, PM2
Secondary finding: yes
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Pathogenic
(Oct 28, 2021)
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criteria provided, single submitter
Method: clinical testing
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MYH7-related skeletal myopathy
Myosin storage myopathy Hypertrophic cardiomyopathy 1 Myopathy, myosin storage, autosomal recessive Congenital myopathy 4A, autosomal dominant Myosin storage myopathy Dilated cardiomyopathy 1S
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000893341.2
First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022 |
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Pathogenic
(Jan 10, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000546214.10
First in ClinVar: Apr 17, 2017 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 906 of the MYH7 protein … (more)
This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 906 of the MYH7 protein (p.Asp906Gly). This variant is present in population databases (rs267606908, gnomAD 0.0009%). This missense change has been observed in individuals with hypertrophic cardiomyopathy (HCM) (PMID: 12081993, 15528230, 24510615, 24704860). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 14125). 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%. Experimental studies have shown that this missense change affects MYH7 function (PMID: 15528230). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Apr 05, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059468.7
First in ClinVar: May 03, 2013 Last updated: Apr 20, 2024 |
Comment:
The p.Asp906Gly variant in MYH7 has been identified in >15 individuals with HCM and segregated with disease in >10 affected relatives from 2 families, although … (more)
The p.Asp906Gly variant in MYH7 has been identified in >15 individuals with HCM and segregated with disease in >10 affected relatives from 2 families, although reduced penetrance was noted in both families (Ho 2002, Alpert 2005, Arad 2005, Kapplinger 2014, LMM data). It has been identified in 1/246244 of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs267606908). This low frequency is consistent with the prevalence and penetrance of the condition in the general population. In vitro functional studies provide some evidence that the p.Asp906Gly variant may impact protein function (Alpert 2005). In addition, the p.Asp906Gly variant was predicted to be pathogenic using a computational tool clinically validated by our laboratory. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). In summary, this variant meets criteria to be classified as pathogenic for HCM in an autosomal dominant manner based upon segregation studies, low frequency in the general population and functional evidence. The ACMG/AMP criteria applied: PS4, PM2, PP1_Strong, PP3. (less)
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Pathogenic
(Nov 01, 2005)
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no assertion criteria provided
Method: literature only
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CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000035442.2
First in ClinVar: Apr 04, 2013 Last updated: Nov 10, 2016 |
Comment on evidence:
In 2 sibs with hypertrophic cardiomyopathy-1 (CMH1; 192600), Arad et al. (2005) identified heterozygosity for an asp906-to-gly (D906G) substitution in the MYH7 gene. The proband … (more)
In 2 sibs with hypertrophic cardiomyopathy-1 (CMH1; 192600), Arad et al. (2005) identified heterozygosity for an asp906-to-gly (D906G) substitution in the MYH7 gene. The proband had apical hypertrophy, whereas the sib, who had sudden death at 45 years of age, was found on necropsy to have massive asymmetrical left ventricular hypertrophy with an interventricular septal thickness greater than 30 mm and a posterior left ventricular wall that was 18 mm thick. Arad et al. (2005) noted that the D906G mutation had previously been identified by Ho et al. (2002) in 22 affected members of a CMH family with a range of maximum left ventricular wall thickness of 13 to 29 mm; none had apical hypertrophy. (less)
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Pathogenic
(Jan 16, 2012)
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no assertion criteria provided
Method: clinical testing
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Not provided
Affected status: not provided
Allele origin:
germline
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Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000280333.1
First in ClinVar: May 29, 2016 Last updated: May 29, 2016 |
Comment:
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 … (more)
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. MYH7 p.Asp906Gly (c.2717A>G) Given the strong case data, strong segregation data, and absence in controls and the general population (reviewed below) we consider this variant very likely disease causing. The variant has been seen in at least 9 unrelated cases of HCM (not including this patient's family). There is strong segregation data. The Seidmans’ group included a kindred with this variant in a study on diastolic dysfunction in HCM (Ho et al 2002). Of 22 carriers studied, 9 had HCM. Alpert et al (2005) reported a family with this variant with 3 of 13 carriers having HCM. Two siblings from this family married two siblings from another family with HCM and a different MYH7 variant. Two offspring carried both variants and both had HCM. The Seidman group later reported a patient with apical HCM and this variant. His brother died suddenly and had evidence of HCM on autopsy (Arad et al 2005). This appears to be a different family than reported in Ho et al (2002). Ackerman's group observed the variant in 4 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). Those cases are presumably redundant with those in another paper by Ackerman’s group that included 5 HCM patients seen at Mayo or tested Transgenomics (Kapplinger et al 2014). McKenna’s group included a patient with HCM and this variant from their UK cohort in a paper on developmental structural differences in HCM (Captur et al 2014). Per their ClinVar submission, LMM considers the variant pathogenic (SCV000059468). The submission does not include any internal case data. 2 additional entries in ClinVar (OMIM and GeneDx) consider this variant pathogenic. In silico analysis with PolyPhen-2 predicts the variant to be benign (HumVar score 0.375). Mutationtaster predicts it to be disease causing. The aspartate at codon 906 is not completely conserved across species. Other variants have been reported in association with disease at this codon (p.Asp906Asn (per ClinVar, LMM considers this of uncertain significance (SCV000059466, last reviewed by LMM in 2010)) and nearby codons (p.Asp900Gly, p.Gln907Lys, p.Leu908Val, p.Ile909Val). In total the variant has not been seen in ~6700 published controls and individuals from publicly available population datasets. There is no variation at codon 906 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6500 Caucasian and African American individuals (as of October 3rd, 2014). Additionally, there is no variation at this codon in the ExAC dataset, which contains sequence data from ~65,000 individuals of varying ancestries from various exome sequencing cohorts (as of Feb 26, 2015). The variant is listed in dbSNP (rs267606908) with the only submission being disease-related (as of October 3rd, 2014). There is also no variation at this codon listed 1000 genomes (as of October 3rd, 2014). The variant was not observed in the following published control samples: 200 (Bos et al 2014). (less)
Number of individuals with the variant: 9
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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The genetic architecture of pediatric cardiomyopathy. | Ware SM | American journal of human genetics | 2022 | PMID: 35026164 |
Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity. | Harper AR | Nature genetics | 2021 | PMID: 33495597 |
Adaptation and validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: recommendations by ClinGen's Inherited Cardiomyopathy Expert Panel. | Kelly MA | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29300372 |
Effects of myosin variants on interacting-heads motif explain distinct hypertrophic and dilated cardiomyopathy phenotypes. | Alamo L | eLife | 2017 | PMID: 28606303 |
The myosin mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations. | Nag S | Nature structural & molecular biology | 2017 | PMID: 28481356 |
The Burden of Early Phenotypes and the Influence of Wall Thickness in Hypertrophic Cardiomyopathy Mutation Carriers: Findings From the HCMNet Study. | Ho CY | JAMA cardiology | 2017 | PMID: 28241245 |
Lack of Phenotypic Differences by Cardiovascular Magnetic Resonance Imaging in MYH7 (β-Myosin Heavy Chain)- Versus MYBPC3 (Myosin-Binding Protein C)-Related Hypertrophic Cardiomyopathy. | Weissler-Snir A | Circulation. Cardiovascular imaging | 2017 | PMID: 28193612 |
Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. | Walsh R | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 27532257 |
Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation. | Homburger JR | Proceedings of the National Academy of Sciences of the United States of America | 2016 | PMID: 27247418 |
Evaluation of the Mayo Clinic Phenotype-Based Genotype Predictor Score in Patients with Clinically Diagnosed Hypertrophic Cardiomyopathy. | Murphy SL | Journal of cardiovascular translational research | 2016 | PMID: 26914223 |
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. | Lopes LR | Heart (British Cardiac Society) | 2015 | PMID: 25351510 |
Abnormal cardiac formation in hypertrophic cardiomyopathy: fractal analysis of trabeculae and preclinical gene expression. | Captur G | Circulation. Cardiovascular genetics | 2014 | PMID: 24704860 |
Distinguishing hypertrophic cardiomyopathy-associated mutations from background genetic noise. | Kapplinger JD | Journal of cardiovascular translational research | 2014 | PMID: 24510615 |
Uptake of cardiac screening and genetic testing among hypertrophic and dilated cardiomyopathy families. | Miller EM | Journal of genetic counseling | 2013 | PMID: 23054336 |
Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy. | Jordan DM | American journal of human genetics | 2011 | PMID: 21310275 |
Impact of multiple gene mutations in determining the severity of cardiomyopathy and heart failure. | Tsoutsman T | Clinical and experimental pharmacology & physiology | 2008 | PMID: 18761664 |
Gene mutations in apical hypertrophic cardiomyopathy. | Arad M | Circulation | 2005 | PMID: 16267253 |
Molecular and phenotypic effects of heterozygous, homozygous, and compound heterozygote myosin heavy-chain mutations. | Alpert NR | American journal of physiology. Heart and circulatory physiology | 2005 | PMID: 15528230 |
Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy. | Ho CY | Circulation | 2002 | PMID: 12081993 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYH7 | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/6a11c78d-e05e-417f-8453-1e66356e09e9 | - | - | - | - |
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Text-mined citations for rs267606908 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.