ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.679G>A (p.Ala227Thr) (rs201828188)

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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, Partners HealthCare Personalized Medicine RCV000151223 SCV000199083 uncertain significance not specified 2013-06-14 criteria provided, single submitter clinical testing The Ala227Thr variant in MYH6 has not been reported in individuals with cardiomy opathy, but has been identified in 1.8% (2/110) of Puerto Rican chromosomes by t he 1000 Genomes Project (dbSNP rs201828188). Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not pro vide strong support for or against an impact to the protein. The presence of thi s variant in the general population raises the possibility that it may be benign but this additional information is needed to establish this with confidence
Ambry Genetics RCV000253650 SCV000318353 likely benign Cardiovascular phenotype 2013-03-14 criteria provided, single submitter clinical testing Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Insufficient or conflicting evidence
Invitae RCV000793999 SCV000933381 uncertain significance Familial hypertrophic cardiomyopathy 14 2018-11-14 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 227 of the MYH6 protein (p.Ala227Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs201828188, ExAC 0.01%). This variant has not been reported in the literature in individuals with MYH6-related disease. ClinVar contains an entry for this variant (Variation ID: 164254). 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: "Tolerated"; 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.

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