ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.343T>C (p.Tyr115His) (rs397516183)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769467 SCV000900862 uncertain significance Cardiomyopathy 2015-11-20 criteria provided, single submitter clinical testing
Invitae RCV000805486 SCV000945443 uncertain significance Hypertrophic cardiomyopathy 2018-12-22 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with histidine at codon 115 of the MYH7 protein (p.Tyr115His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is present in population databases (rs397516183, ExAC 0.001%). This variant has been observed in individuals affected with hypertrophic cardiomyopathy (PMID: 15358028, 27247418, 27532257). ClinVar contains an entry for this variant (Variation ID: 42960). 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000805486 SCV000059504 likely pathogenic Hypertrophic cardiomyopathy 2019-02-08 criteria provided, single submitter clinical testing The p.Tyr115His variant in MYH7 has been reported in 7 individuals with hypertro phic cardiomyopathy (HCM) (Van Driest 2004, Homburger 2016, Walsh 2017). It has also been identified in 1/113572 European chromosomes by gnomAD (http://gnomad.b roadinstitute.org). Computational prediction tools and conservation analysis sug gest that this variant may impact the protein, though this information is not pr edictive enough to determine pathogenicity. In summary, although additional stud ies are required to fully establish its clinical significance, this variant meet s criteria to be classified as likely pathogenic for autosomal dominant HCM. ACM G/AMP Criteria applied: PM2, PS4_Moderate, PP3, PS3_Supporting.

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