ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3715G>A (p.Glu1239Lys)

gnomAD frequency: 0.00001  dbSNP: rs267602904
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000794599 SCV000934017 uncertain significance Hypertrophic cardiomyopathy 2024-05-06 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1239 of the MYBPC3 protein (p.Glu1239Lys). This variant is present in population databases (rs267602904, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 78394). 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.
All of Us Research Program, National Institutes of Health RCV000794599 SCV004842544 uncertain significance Hypertrophic cardiomyopathy 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 1239 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 was reported in one stillbirth without chromosomal abnormalities (PMID: 30615648). This variant has been identified in 2/249230 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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