ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.1138G>A (p.Glu380Lys)

dbSNP: rs768924353
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001231664 SCV001404193 uncertain significance Hypertrophic cardiomyopathy 14 2022-09-03 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 380 of the MYH6 protein (p.Glu380Lys). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 958487). This missense change has been observed in individual(s) with sudden cardiac arrest (PMID: 30975432). This variant is not present in population databases (gnomAD no frequency).
Fulgent Genetics, Fulgent Genetics RCV002497791 SCV002789463 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-08-31 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004538485 SCV004711523 uncertain significance MYH6-related disorder 2023-11-07 no assertion criteria provided clinical testing The MYH6 c.1138G>A variant is predicted to result in the amino acid substitution p.Glu380Lys. This variant has been reported as de novo in an individual with double outlet right ventricle (Tables S2, Hayes et al. 2023. PubMed ID: 37417234). This variant has also been reported in an individual with sudden cardiac arrest (Asatryan et al. 2019. PubMed ID: 30975432). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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