ClinVar Miner

Submissions for variant NM_000432.4(MYL2):c.275G>T (p.Gly92Val)

dbSNP: rs727503297
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Total submissions: 2
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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 RCV000151362 SCV000199348 uncertain significance not specified 2018-11-23 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Gly92Val variant in MYL2 has been identified by our laboratory in 1 neonate with HCM and segregated with disease in 4 affected relatives. It was absent from large popula tion studies. Computational prediction tools and conservation analysis suggest t hat this variant may impact the protein. In addition, this variant is located in the first base of the exon, which is part of the 3? splice region and splicing computational tools predict a splicing impact. However, predictions from computa tional tools are not predictive enough to determine pathogenicity. In summary, w hile there is some suspicion for a pathogenic role, the clinical significance of the p.Gly92Val variant is uncertain. ACMG/AMP Criteria applied: PM2, PP1, PP3.
Labcorp Genetics (formerly Invitae), Labcorp RCV002516041 SCV003441654 uncertain significance Hypertrophic cardiomyopathy 10 2022-02-19 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 92 of the MYL2 protein (p.Gly92Val). This variant is not present in population databases (gnomAD no frequency). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 164476). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257).

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