Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000422482 | SCV000533140 | likely pathogenic | not provided | 2016-11-03 | criteria provided, single submitter | clinical testing | The C1386Y variant in the SCN2A gene has not been reported previously as a pathogenic variant, noras a benign variant, to our knowledge. The C1386Y variant was not observed in approximately 6500individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. The C1386Y variant is anon-conservative amino acid substitution, which is likely to impact secondary protein structure asthese residues differ in polarity, charge, size and/or other properties. This substitution occurs withinthe pore forming loop between the S5 and S6 transmembrane segments at a position that is conservedacross species. In silico analysis predicts this variant is probably damaging to the proteinstructure/function. The C1386Y variant is a strong candidate for a pathogenic variant however thepossibility it may be a rare benign variant cannot be excluded. |