ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3142C>T (p.Arg1048Cys)

gnomAD frequency: 0.00001  dbSNP: rs11570113
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000617909 SCV000736193 uncertain significance Cardiovascular phenotype 2022-08-31 criteria provided, single submitter clinical testing The p.R1048C variant (also known as c.3142C>T), located in coding exon 29 of the MYBPC3 gene, results from a C to T substitution at nucleotide position 3142. The arginine at codon 1048 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well 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.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000626632 SCV000747333 uncertain significance Hypertrophic cardiomyopathy 2017-01-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001181072 SCV001346145 uncertain significance Cardiomyopathy 2021-11-30 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 1048 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 3/241846 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 RCV000626632 SCV002944446 uncertain significance Hypertrophic cardiomyopathy 2023-06-17 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 518771). This variant is present in population databases (rs11570113, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1048 of the MYBPC3 protein (p.Arg1048Cys).

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