ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4725G>T (p.Lys1575Asn)

dbSNP: rs45476496
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001774886 SCV002004190 uncertain significance not provided 2019-11-04 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Labcorp Genetics (formerly Invitae), Labcorp RCV001868688 SCV002249511 uncertain significance Hypertrophic cardiomyopathy 2021-09-18 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 1575 of the MYH7 protein (p.Lys1575Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. 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: "Probably 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.
All of Us Research Program, National Institutes of Health RCV004009033 SCV004829099 uncertain significance Cardiomyopathy 2023-06-26 criteria provided, single submitter clinical testing This missense variant replaces lysine with asparagine at codon 1575 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 not been identified 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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