Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Genetics and Molecular Cardiology, |
RCV000201500 | SCV000256173 | likely pathogenic | Hypertrophic cardiomyopathy 4 | criteria provided, single submitter | clinical testing | ||
DASA | RCV004553097 | SCV002097310 | pathogenic | MYBPC3-related disorder | 2022-02-14 | criteria provided, single submitter | clinical testing | The c.3662del;p.(Leu1221Argfs*16) is a null frameshift variant in the MYBPC3 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevant exon to the transcript -PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 407321) - PS4_supporting. This variant is not present in population databases (rs863225107, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic. |
Labcorp Genetics |
RCV001853228 | SCV002173787 | pathogenic | Hypertrophic cardiomyopathy | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu1221Argfs*16) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 24093860, 30297972). ClinVar contains an entry for this variant (Variation ID: 217479). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV004649095 | SCV005145672 | pathogenic | Cardiovascular phenotype | 2024-05-06 | criteria provided, single submitter | clinical testing | The c.3662delT pathogenic mutation, located in coding exon 33 of the MYBPC3 gene, results from a deletion of one nucleotide at nucleotide position 3662, causing a translational frameshift with a predicted alternate stop codon (p.L1221Rfs*16). This alteration has been reported in hypertrophic cardiomyopathy (HCM) cohort (Marsiglia JD et al. Am Heart J, 2013 Oct;166:775-82; Ho CY et al. Circulation, 2018 Oct;138:1387-1398). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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. |