Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000480153 | SCV000569612 | likely pathogenic | not provided | 2016-03-16 | criteria provided, single submitter | clinical testing | A novel W308S variant that is likely pathogenic has been identified in the KCNQ3 gene. The W308S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 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 W308S 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. Additionally, 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. Furthermore, missense variants in nearby residues (D305G, W309R, G310V) have been reported in the Human Gene Mutation Database in association with KCNQ3-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Gene |
RCV001814160 | SCV002061348 | not provided | Seizures, benign familial neonatal, 2 | no assertion provided | literature only | Mother (not tested) with neonatal and febrile seizures |