ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1141G>A (p.Ala381Thr)

dbSNP: rs727504753
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Cardiomyopathy Variant Curation Expert Panel RCV001727606 SCV001976470 uncertain significance Hypertrophic cardiomyopathy 2021-09-22 reviewed by expert panel curation The NM_000257.4(MYH7):c.1141G>A (p.Ala381Thr) variant has been identified in 1 neonate with HCM and repolarization abnormalities (LMM pers. comm.); however this case data is insufficient to apply PS4. This variant was absent from large population studies (PM2; gnomAD v2.1.1, http://gnomad.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 associated with HCM (PM1; Walsh 2017 PMID:27532257). Computational prediction tools and conservation analysis were mixed about the potential impact of this variant. In summary, due to insufficient evidence, this variant is classified as uncertain significance for hypertrophic cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): PM2, PM1.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156061 SCV000205774 uncertain significance not specified 2013-08-29 criteria provided, single submitter clinical testing The Ala381Thr variant in MYH7 has not been previously reported in individuals wi th cardiomyopathy or in large population studies. Computational analyses (bioche mical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do no t provide strong support for or against an impact to the normal function of the protein. At this time, additional information is needed to fully assess the clin ical significance of the Ala381Thr variant.
Baylor Genetics RCV000850503 SCV000992705 likely pathogenic Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy 2018-10-12 criteria provided, single submitter clinical testing

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