ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1477_1478del (p.Met493fs)

dbSNP: rs727504336
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Cardiomyopathy Variant Curation Expert Panel RCV000154450 SCV000564416 uncertain significance Cardiomyopathy 2021-11-30 reviewed by expert panel curation The NM_000257.3(MYH7):c.1477_1478delAT (p.Met493Valfs) variant has been identified in 1 individual with features of both HCM and DCM (Zimmerman 2010 PMID:20474083; Walsh 2017 PMID: 27532257, LMM pers. comm.) however, this is insufficient to apply the PS4 criterion. This variant was absent from large population studies (PM2; http:// gnomad.broadinstitute.org, v.2.1.1). This variant is predicted to cause a frameshift leading to a truncated or absent protein. The contribution of loss of function (LOF) variants in MYH7 to autosomal dominant inherited cardiomyopathy is incompletely understood therefore PVS1 was not applied. In summary, due to insufficient evidence, this variant meets criteria to be classified as uncertain significance for cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): PM2.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000599624 SCV000204119 likely pathogenic Primary dilated cardiomyopathy 2016-04-26 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Invitae RCV001850113 SCV002225798 uncertain significance Hypertrophic cardiomyopathy 2021-08-07 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 177817). This premature translational stop signal has been observed in individual(s) with clinical features of MYH7-related conditions (PMID: 20474083, 27532257). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Met493Valfs*19) in the MYH7 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MYH7 cause disease.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000154450 SCV004239437 uncertain significance Cardiomyopathy 2023-05-12 criteria provided, single submitter clinical testing

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