Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000485952 | SCV000574102 | likely pathogenic | not provided | 2017-03-16 | criteria provided, single submitter | clinical testing | A variant that is likely pathogenic has also been identified in the ISPD gene. The R205C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, a different variant at the same position (R205H) has been reported previously in an individual with Walker-Warburg syndrome who had a deletion on the opposite ISPD allele (Czeschik et al., 2013). The R205C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R205C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |