Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clinical Genetics Service, |
RCV001542097 | SCV001759958 | likely pathogenic | Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2 | 2021-07-22 | no assertion criteria provided | clinical testing | The Arg274 residue is located in the protease domain of the protein and is highly conserved among different species and other members of the HtrA family. It is located nearby the highly conserved Phe-278 residue, involved in the homotrimerization of the protein. This change is classified as likely pathogenic following the ACMG criteria: (i) it is absent in several population databases; (ii) another missense variant affecting the same residue has been classified as pathogenic; (iii) the 15/15 in silico consulted predictors of pathogenicity indicate the variant as “likely pathogenic†and 4/4 protein stability consulted tools predict a potentially deleterious effect ; (iv) the amino acid residue is located in the protease domain where pathogenic variants were already found; (v) the amino acid residue is located adjacent to the protein-protein binding site of the enzyme and is highly evolutionary conserved; (vi) segregation analysis was positive in several affected member. |