Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158483 | SCV000208418 | pathogenic | Cardiomyopathy | 2011-12-20 | criteria provided, single submitter | clinical testing | A deletion of a single “C” nucleotide in exon 30 of the MYBPC3 gene. The normal sequence with the base that is deleted in braces is: AGAC{C}ATGG. This mutation is denoted c.3327delC at the cDNA level or p.Met1110TrpfsX79 at the protein level. The c.3327delC mutation in the MYBPC3 gene causes a shift in reading frame at codon Methionine 1110, changing it to a Tryptophan, and creates a premature Stop codon at position 79 of the new reading frame. Although this mutation has not been reported previously to our knowledge, it is expected to result in an abnormal, truncated protein or in absence of protein from this allele due to mRNA decay, and therefore is interpreted to be a disease-causing mutation.The variant is found in HCM panel(s). |
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000623596 | SCV000740353 | pathogenic | not provided | 2016-05-18 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV004786427 | SCV005399129 | pathogenic | Hypertrophic cardiomyopathy 4 | 2022-03-31 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with hypertrophic cardiomyopathy 4 (HCM; MIM#115197). (I) 0108 - This gene is associated with both recessive and dominant disease. Dominant inheritance is frequently reported in adult onset conditions, however recessive inheritance results in a more severe early onset phenotype (OMIM). (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 32841044). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been classified as pathogenic, and observed in individuals with hypertrophic cardiomyopathy (PMID: 32268277, PMID: 28771489, ClinVar). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |