ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2456T>C (p.Met819Thr)

dbSNP: rs876657870
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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 RCV000217600 SCV000271990 uncertain significance not specified 2016-03-17 criteria provided, single submitter clinical testing The p.Met819Thr variant in MYBPC3 has not been previously reported in individual s with cardiomyopathy or in large population studies. Computational prediction t ools and conservation analysis suggest that the p.Met819Thr variant may impact t he protein, though this information is not predictive enough to determine pathog enicity. In summary, the clinical significance of the p.Met819Thr variant is unc ertain.
Invitae RCV001203789 SCV001374966 uncertain significance Hypertrophic cardiomyopathy 2023-08-07 criteria provided, single submitter clinical testing An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. ClinVar contains an entry for this variant (Variation ID: 228866). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 33782553). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 819 of the MYBPC3 protein (p.Met819Thr).
Color Diagnostics, LLC DBA Color Health RCV001525836 SCV001736033 uncertain significance Cardiomyopathy 2023-05-25 criteria provided, single submitter clinical testing This missense variant replaces methionine with threonine at codon 819 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 32841044, 33782553). This variant has been identified in 1/249246 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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