Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000485871 | SCV000570401 | likely pathogenic | not provided | 2017-01-26 | criteria provided, single submitter | clinical testing | A novel I760F variant that is likely pathogenic has been identified in the KCNT1 gene. The I760F 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. This substitution occurs at a position that is conserved across species, and a different missense variant at the same codon (I760M) has been previously reported in an individual with malignant migrating partial seizures of infancy (Barcia et al., 2012). In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the I760F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |