ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1604T>C (p.Leu535Pro)

gnomAD frequency: 0.00004  dbSNP: rs730880548
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158103 SCV000208038 uncertain significance not provided 2022-07-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002399568 SCV002709565 uncertain significance Cardiovascular phenotype 2021-06-14 criteria provided, single submitter clinical testing The p.L535P variant (also known as c.1604T>C), located in coding exon 17 of the MYBPC3 gene, results from a T to C substitution at nucleotide position 1604. The leucine at codon 535 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. 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 RCV002515064 SCV003033487 uncertain significance Hypertrophic cardiomyopathy 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 535 of the MYBPC3 protein (p.Leu535Pro). This variant is present in population databases (rs730880548, gnomAD 0.007%). 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: 180945). 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.

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