Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV001195422 | SCV001365773 | likely pathogenic | Congenital adrenal insuffiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency | 2019-07-25 | criteria provided, single submitter | clinical testing | The p.Gln131X variant in CYP11A1 has not been previously reported in individuals with adrenal insufficiency and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 131, which is predicted to lead to a truncated or absent protein. Loss of function of the CYP11A1 gene is an established disease mechanism in autosomal recessive congenital adrenal insufficiency. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive congenital adrenal insufficiency. ACMG/AMP Criteria applied: PVS1, PM2. |