ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.936C>A (p.Phe312Leu)

dbSNP: rs771522982
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000845426 SCV000987499 uncertain significance Primary familial dilated cardiomyopathy criteria provided, single submitter clinical testing
GeneDx RCV001776064 SCV002013090 uncertain significance not provided 2019-08-06 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Fulgent Genetics, Fulgent Genetics RCV002487877 SCV002780102 uncertain significance Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy 2021-10-17 criteria provided, single submitter clinical testing
Invitae RCV002536167 SCV003468619 uncertain significance Hypertrophic cardiomyopathy 2022-06-03 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 312 of the MYH7 protein (p.Phe312Leu). This variant is present in population databases (rs771522982, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 684823). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Revvity Omics, Revvity RCV001776064 SCV003817714 uncertain significance not provided 2019-03-21 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004002897 SCV004822527 uncertain significance Cardiomyopathy 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces phenylalanine with leucine at codon 312 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 1/251404 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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