ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.362C>T (p.Pro121Leu) (rs551888783)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522511 SCV000619318 uncertain significance not provided 2017-07-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYBPC3 gene. The P121L variant has not been published as pathogenic or benign in association with cardiomyopathy to our knowledge. This variant is observed in 1/1790 (0.06%) alleles from individuals of East Asian ancestry and in 2/8480 alleles from individuals of South Asian ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P121L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved across species and leucine (L) is the wild-type residue at this position in multiple mammalian species. Additionally, in silico analysis predicts this variant likely does not alter the protein structure/function.
Invitae RCV000695171 SCV000823654 uncertain significance Hypertrophic cardiomyopathy 2020-10-13 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 121 of the MYBPC3 protein (p.Pro121Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs551888783, ExAC 0.06%). This variant has not been reported in the literature in individuals with MYBPC3-related disease. ClinVar contains an entry for this variant (Variation ID: 450709). An algorithm developed specifically for the MYBPC3 gene suggests that this missense change is likely to be tolerated (PMID: 21310275). However, this prediction has not been confirmed by published functional studies and its clinical significance is uncertain. 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.
Color Health, Inc RCV000772059 SCV000905087 likely benign Cardiomyopathy 2018-10-04 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845439 SCV000987514 uncertain significance Primary familial dilated cardiomyopathy criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000772059 SCV001333007 uncertain significance Cardiomyopathy 2018-09-18 criteria provided, single submitter clinical testing

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