ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1039G>A (p.Gly347Ser)

gnomAD frequency: 0.00001  dbSNP: rs397515884
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Total submissions: 6
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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 RCV000035367 SCV000059015 uncertain significance not specified 2019-08-02 criteria provided, single submitter clinical testing The p.Gly347Ser variant in MYBPC3 has been identified in 1 individual with DCM (LMM data) and 3/112736 European chromosomes by gnomAD (https://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2.
Invitae RCV001344496 SCV001538554 uncertain significance Hypertrophic cardiomyopathy 2023-01-10 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 347 of the MYBPC3 protein (p.Gly347Ser). 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 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 42502). This missense change has been observed in individual(s) with clinical features of hypertrophic cardiomyopathy (PMID: 33673806). This variant is present in population databases (rs397515884, gnomAD 0.003%).
PreventionGenetics, part of Exact Sciences RCV003390722 SCV004119726 uncertain significance MYBPC3-related condition 2022-11-16 criteria provided, single submitter clinical testing The MYBPC3 c.1039G>A variant is predicted to result in the amino acid substitution p.Gly347Ser. This variant was reported in an individual with hypertrophic cardiomyopathy (Additional file 2, Hathaway et al. 2021. PubMed ID: 33673806). This variant is reported in 0.0027% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-47367809-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Blueprint Genetics RCV000157306 SCV000207038 likely pathogenic Primary familial hypertrophic cardiomyopathy 2014-05-22 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV001699104 SCV001925172 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001699104 SCV001968222 uncertain significance not provided no assertion criteria provided clinical testing

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