ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.46C>T (p.Pro16Ser)

gnomAD frequency: 0.00001  dbSNP: rs730880573
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158175 SCV000208110 uncertain significance not provided 2023-04-27 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; 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
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000158175 SCV000712383 uncertain significance not provided 2019-04-05 criteria provided, single submitter clinical testing The p.Pro16Ser variant in MYBPC3 has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/47636 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs730880573). Computational prediction tools and conservation analysis suggest that the variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Pro16Ser variant is uncertain.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV005400710 SCV000987400 uncertain significance Cardiovascular phenotype 2025-04-08 criteria provided, single submitter clinical testing PM2, PS4_supp
Labcorp Genetics (formerly Invitae), Labcorp RCV001352035 SCV001546558 uncertain significance Hypertrophic cardiomyopathy 2024-12-17 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 16 of the MYBPC3 protein (p.Pro16Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 180979). 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.
Fulgent Genetics, Fulgent Genetics RCV002505187 SCV002815147 uncertain significance Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 2022-04-14 criteria provided, single submitter clinical testing

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