ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1601C>T (p.Ala534Val)

gnomAD frequency: 0.00003  dbSNP: rs374349666
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001176552 SCV001340571 uncertain significance Cardiomyopathy 2022-10-11 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 534 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 cardiovascular disorders in the literature. This variant has been identified in 8/245062 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.
Invitae RCV001315140 SCV001505697 uncertain significance Hypertrophic cardiomyopathy 2023-10-18 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 534 of the MYBPC3 protein (p.Ala534Val). This variant is present in population databases (rs374349666, gnomAD 0.02%). This missense change has been observed in individual(s) with cardiomyopathy (PMID: 28679633). ClinVar contains an entry for this variant (Variation ID: 918779). 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. Studies have shown that this missense change does not affect mRNA splicing (PMID: 28679633). 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.
GeneDx RCV001732061 SCV001982616 uncertain significance not provided 2021-09-07 criteria provided, single submitter clinical testing Reported in association with cardiomyopathy (Ito et al., 2017); however, specific clinical information was not provided; In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 918779; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 28679633)
Ambry Genetics RCV002402528 SCV002706381 uncertain significance Cardiovascular phenotype 2019-07-30 criteria provided, single submitter clinical testing The p.A534V variant (also known as c.1601C>T), located in coding exon 17 of the MYBPC3 gene, results from a C to T substitution at nucleotide position 1601. The alanine at codon 534 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002491501 SCV002782115 uncertain significance Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 2021-12-05 criteria provided, single submitter clinical testing

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