ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.467T>C (p.Leu156Pro)

gnomAD frequency: 0.00001  dbSNP: rs730880616
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000822462 SCV000963264 uncertain significance Hypertrophic cardiomyopathy 2022-05-11 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 156 of the MYBPC3 protein (p.Leu156Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 21750094). ClinVar contains an entry for this variant (Variation ID: 181036). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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.
Color Diagnostics, LLC DBA Color Health RCV001178626 SCV001343118 uncertain significance Cardiomyopathy 2023-04-07 criteria provided, single submitter clinical testing This missense variant replaces leucine with proline at codon 156 of the MYBPC3 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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: 21750094) and in an individual affected with an unspecified cardiomyopathy (PMID: 33764162). This variant has not been identified 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001507793 SCV001713572 uncertain significance not provided 2020-10-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002336349 SCV002638176 uncertain significance Cardiovascular phenotype 2020-02-14 criteria provided, single submitter clinical testing The p.L156P variant (also known as c.467T>C), located in coding exon 4 of the MYBPC3 gene, results from a T to C substitution at nucleotide position 467. The leucine at codon 156 is replaced by proline, an amino acid with similar properties. This variant was reported in an individual with hypertrophic cardiomyopathy; however, clinical details were limited (Waldm&uuml;ller S et al. Eur. J. Heart Fail., 2011 Nov;13:1185-92). This amino acid position is highly conserved in available 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.

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