ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3683G>C (p.Arg1228Pro)

dbSNP: rs528940575
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766377 SCV000208188 uncertain significance not provided 2023-11-29 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32746448)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000158253 SCV000271994 uncertain significance not specified 2015-03-23 criteria provided, single submitter clinical testing The p.Arg1228Pro variant in MYBPC3 has not been previously reported in individua ls with cardiomyopathy or in large population studies. Arginine (Arg) at positio n 1228 is conserved in mammals but not in evolutionarily distant species. Additi onal computational prediction tools suggest that this variant may impact the pro tein, though this information is not predictive enough to determine pathogenicit y. In summary, the clinical significance of the p.Arg1228Pro variant is uncertai n.
Ambry Genetics RCV002453542 SCV002615279 uncertain significance Cardiovascular phenotype 2021-12-15 criteria provided, single submitter clinical testing The p.R1228P variant (also known as c.3683G>C), located in coding exon 33 of the MYBPC3 gene, results from a G to C substitution at nucleotide position 3683. The arginine at codon 1228 is replaced by proline, an amino acid with dissimilar properties. This alteration has been reported in a pediatric cardiomyopathy cohort (Burstein DS et al. Pediatr Res, 2021 05;89:1470-1476). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV003998349 SCV004837659 uncertain significance Hypertrophic cardiomyopathy 2023-11-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003998349 SCV005732673 uncertain significance Hypertrophic cardiomyopathy 2024-10-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1228 of the MYBPC3 protein (p.Arg1228Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32746448). ClinVar contains an entry for this variant (Variation ID: 181018). 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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