ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2785_2787GAG[2] (p.Glu931del) (rs397516172)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Inherited Cardiomyopathy Variant Curation Expert Panel, RCV000707732 SCV000564439 likely pathogenic Hypertrophic cardiomyopathy 2016-12-15 reviewed by expert panel curation The c.2791_2793del (p.Glu931del) variant in MYH7 has been reported in 4 individuals with hypertrophic cardiomyopathy (PS4_Supporting; PMID:9829907; PMID:12707239; PMID:27532257; Partners LMM ClinVar SCV000059478.5). This variant segregated with disease in 5 affected individuals (PP1_Moderate; PMID:9829907). This variant was absent from large population studies (PM2; This variant is a deletion of 1 amino acid at position 931 and is not predicted to alter the protein reading-frame (PM4). In summary, this variant meets criteria to be classified as likely pathogenic for hypertrophic cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): PM2; PM4; PP1_Moderate; PS4_ Supporting
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000707732 SCV000059478 likely pathogenic Hypertrophic cardiomyopathy 2014-04-14 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000158830 SCV000208765 pathogenic not provided 2014-12-04 criteria provided, single submitter clinical testing The c.2791_2793delGAG mutation in the MYH7 gene has been reported in one family with HCM (reported as E930 due to alternate nomenclature) (Tesson F et al., 1998). Multiple affected individuals in this family were identified to harbor c.2791_2793delGAG and it was absent from 100 control individuals. c.2791_2793delGAG results in an in-frame deletion of a Glutamic acid at codon 931 in the MYH7 gene. Other in-frame deletions in the MYH7 gene have been reported in association with HCM. In summary, c.2791_2793delGAG in the MYH7 gene is interpreted as a disease-causing mutation.
Invitae RCV000707732 SCV000836841 pathogenic Hypertrophic cardiomyopathy 2018-01-19 criteria provided, single submitter clinical testing This variant, c.2791_2793delGAG, results in the deletion of 1 amino acid(s) of the MYH7 protein (p.Glu931del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with hypertrophic cardiomyopathy (HCM) (PMID: 27532257) and has been described to segregate with disease in a family (PMID: 9829907). This variant is also known as Glu930 codon deletion in the literature. ClinVar contains an entry for this variant (Variation ID: 42934). Two different missense substitutions at this codon (p.Glu931Gly and p.Glu931Lys) have been determined to be pathogenic (PMID: 25351510, 15358028, 24111713). This suggests that the glutamic acid residue is critical for MYH7 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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