Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000484946 | SCV000570492 | likely pathogenic | not provided | 2016-05-25 | criteria provided, single submitter | clinical testing | The S314P 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 S314P 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 alters a conserved position predicted to be within the C-terminal cytoplasmic domain, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense variants in nearby residues (A309V, G315R, K319T) have been reported in the Human Gene Mutation Database in association with KCNQ2-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. |