ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3357C>A (p.Tyr1119Ter)

dbSNP: rs1565622952
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000702518 SCV000831376 pathogenic Hypertrophic cardiomyopathy 2022-11-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 579276). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr1119*) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547).
Genetics and Molecular Pathology, SA Pathology RCV000702518 SCV004175502 pathogenic Hypertrophic cardiomyopathy 2023-06-14 criteria provided, single submitter clinical testing The MYBPC3 c.3357C>A variant is classified as Pathogenic (PVS1, PS4_Supporting, PM2) The MYBPC3 c.3357C>A variant is a single nucleotide change which is predicted to result in premature termination of the protein product at codon 1119, resulting in loss of function. Loss of function of MYBPC3 is a known disease mechanism in hypertrophic cardiomyopathy (HCM) (PVS1). This variant has been reported in 2 probands with a clinical presentation of HCM (PMID#27532257, Invitae) (PS4_Supporting). This variant is absent from population databases (PM2), is reported in dbSNP (rs1565622952), is reported as disease causing in HGMD (CM1616656) and and has been reported as pathogenic by other diagnostic laboratories (ClinVar Variation ID: 579276).
Ambry Genetics RCV004026598 SCV005033744 pathogenic Cardiovascular phenotype 2023-10-16 criteria provided, single submitter clinical testing The p.Y1119* pathogenic mutation (also known as c.3357C>A), located in coding exon 31 of the MYBPC3 gene, results from a C to A substitution at nucleotide position 3357. This changes the amino acid from a tyrosine to a stop codon within coding exon 31. This variant has been detected in hypertrophic cardiomyopathy (HCM) cohorts, or cohorts submitted for HCM genetic testing (Walsh R et al. Genet Med, 2017 Feb;19:192-203; Magrì D et al. J Clin Med, 2020 May;9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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