ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.355G>A (p.Glu119Lys)

gnomAD frequency: 0.00001  dbSNP: rs397516025
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017295 SCV000059247 uncertain significance not provided 2023-05-10 criteria provided, single submitter clinical testing The p.Glu119Lys variant in MYBPC3 has been reported in 2 individuals with hypertrophic cardiomyopathy (HCM) and segregated with disease in 2 affected relatives, but not in another affected family member from 1 family (Walsh 2017 PMID: PMID: 27532257, LMM data). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID 42721) and was absent from large population studies. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_supporting, PS4_supporting, BP4.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170429 SCV001333008 uncertain significance Cardiomyopathy 2018-06-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001852723 SCV002116984 uncertain significance Hypertrophic cardiomyopathy 2025-01-20 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 119 of the MYBPC3 protein (p.Glu119Lys). This variant is present in population databases (rs397516025, gnomAD 0.003%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 42721). 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. 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.
Dept of Medical Biology, Uskudar University RCV003318338 SCV004021976 uncertain significance Long QT syndrome 2024-01-08 criteria provided, single submitter research Criteria: PM2, BP4

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