ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2035C>T (p.Pro679Ser)

gnomAD frequency: 0.00001  dbSNP: rs372493586
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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 RCV001187130 SCV001353815 uncertain significance Cardiomyopathy 2023-08-16 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 679 of the MYBPC3 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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). 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.
Invitae RCV001850017 SCV002136316 uncertain significance Hypertrophic cardiomyopathy 2022-08-04 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 161302). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 21750094). This variant is present in population databases (rs372493586, gnomAD 0.0009%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 679 of the MYBPC3 protein (p.Pro679Ser).
Ambry Genetics RCV003298152 SCV003993413 uncertain significance Cardiovascular phenotype 2023-04-27 criteria provided, single submitter clinical testing The p.P679S variant (also known as c.2035C>T), located in coding exon 21 of the MYBPC3 gene, results from a C to T substitution at nucleotide position 2035. The proline at codon 679 is replaced by serine, an amino acid with similar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Waldmüller 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.
CSER _CC_NCGL, University of Washington RCV000148659 SCV000190383 uncertain significance Primary familial hypertrophic cardiomyopathy 2014-06-01 no assertion criteria provided research

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