ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3781G>A (p.Glu1261Lys)

gnomAD frequency: 0.00001  dbSNP: rs730880141
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001183484 SCV001349228 uncertain significance Cardiomyopathy 2023-08-02 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 1261 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 not been reported in individuals affected with MYBPC3-related disorders in the literature. This variant has been identified in 3/248532 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.
Ambry Genetics RCV002345529 SCV002622555 uncertain significance Cardiovascular phenotype 2021-03-09 criteria provided, single submitter clinical testing The p.E1261K variant (also known as c.3781G>A), located in coding exon 33 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 3781. The glutamic acid at codon 1261 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, lysine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV002516356 SCV003512920 uncertain significance Hypertrophic cardiomyopathy 2023-11-17 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 1261 of the MYBPC3 protein (p.Glu1261Lys). This variant is present in population databases (rs730880141, gnomAD 0.009%). 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: 180414). 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 tolerated. 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.
Blueprint Genetics RCV000157322 SCV000207057 uncertain significance Primary familial hypertrophic cardiomyopathy 2014-11-11 no assertion criteria provided clinical testing

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