Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000439038 | SCV000521257 | likely pathogenic | not provided | 2016-10-31 | criteria provided, single submitter | clinical testing | The P694L variant in the OSMR gene has been reported previously in the heterozygous state, in multiple individuals with familial and sporadic primary cutaneous amyloidosis (Lin et al., 2010; Schreml et al., 2013). The P694L variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P694L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, we interpret P694L as a likely pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |
OMIM | RCV000023144 | SCV000044435 | pathogenic | Amyloidosis, primary localized cutaneous, 1 | 2010-01-01 | no assertion criteria provided | literature only |