Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158243 | SCV000208178 | likely pathogenic | not provided | 2012-03-06 | criteria provided, single submitter | clinical testing | The Pro1181Ala variant in the MYBPC3 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. Pro1181Ala results in a semi-conservative substitution of a Proline residue with an Alanine residue at a position that is conserved across species throughout evolution. In silico analysis predicts Pro1181Ala is probably damaging to the protein structure/function and disease-causing (4-6). In addition, mutations in nearby codons (Tyr1172Cys, Thr1184Asn, Leu1187Arg) have been reported in association with HCM, supporting the functional importance of this region of the protein (7). The NHLBI ESP Exome Variant Server reports Arg845Pro was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations (8).In summary, the Pro1181Ala variant in the MYBPC3 gene is a good candidate for a disease-causing mutation, however we cannot unequivocally determine whether Pro1181Ala is a pathogenic mutation or a benign variant. Mutations in MYBPC3 have been reported in 20%-30% of patients with autosomal dominant familial hypertrophic cardiomyopathy. The variant is found in HCM panel(s). |