ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2677G>A (p.Ala893Thr)

gnomAD frequency: 0.00001  dbSNP: rs750204313
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001176922 SCV001341022 uncertain significance Cardiomyopathy 2018-12-07 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant is located in the neck and hinge (S2) domain of the MYH7 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/276282 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Labcorp Genetics (formerly Invitae), Labcorp RCV001875829 SCV002110783 uncertain significance Hypertrophic cardiomyopathy 2021-04-16 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This missense change is located in a region of the MYH7 protein where a significant number of previously reported MYH7 missense mutations are found (PMID: 27532257). These observations suggest that this may be a clinically significant region of the protein. This variant has not been reported in the literature in individuals with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 918999). This variant is present in population databases (rs750204313, ExAC 0.01%). This sequence change replaces alanine with threonine at codon 893 of the MYH7 protein (p.Ala893Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine.
Fulgent Genetics, Fulgent Genetics RCV002483960 SCV002786119 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 2021-09-13 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003130173 SCV003817703 uncertain significance not provided 2021-05-28 criteria provided, single submitter clinical testing

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