Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000768481 | SCV000886772 | likely pathogenic | Hypertrophic cardiomyopathy | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000768481 | SCV004848094 | pathogenic | Hypertrophic cardiomyopathy | 2017-09-07 | criteria provided, single submitter | clinical testing | The p.Thr1184fs variant in MYBPC3 has not been previously reported in individuals with cardiomyopathy and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1184 and leads to a premature termination codon 24 amino acids downstream. This alteration is predicted to lead to a truncated or absent protein. Nonsense and other MYBPC3 variants resulting in a heterozygous loss of function are strongly associated with HCM. In summary, this variant meets criteria to be classified as pathogenic for HCM in an autosomal dominant manner based upon the predicted impact on the protein and absence from control databases. |