ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.485A>G (p.Tyr162Cys)

gnomAD frequency: 0.00002  dbSNP: rs397516772
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037518 SCV000061176 uncertain significance not specified 2012-12-04 criteria provided, single submitter clinical testing The Tyr162Cys variant in MYH6 has not been reported in the literature, but has b een identified in an African American infant with DCM tested by our laboratory ( LMM unpublished data). This variant has not been identified in large and broad E uropean American and African American populations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/), though this low frequency is insuff icient to assess the clinical significance of this variant. The same variant in MYH7, a homolog with high sequence similarity, has been identified in cases of H CM and some studies suggest that it could impact the protein (Rayment 1995, Cuda 1997). However, due to the similarity between these genes, we cannot rule out t hat these reports detected this variant (in MYH6). Computational analyses (bioch emical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) sugg est that this variant may impact the protein, though this information is not pre dictive enough to determine pathogenicity. In summary, additional information is needed to assess the clinical significance of this variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000459581 SCV000546158 uncertain significance Hypertrophic cardiomyopathy 14 2023-04-07 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. This variant is present in population databases (rs397516772, gnomAD 0.007%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 44523). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH6 protein function. This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 162 of the MYH6 protein (p.Tyr162Cys).
Fulgent Genetics, Fulgent Genetics RCV002496593 SCV002813409 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-10-20 criteria provided, single submitter clinical testing

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