Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000414649 | SCV000491949 | uncertain significance | not specified | 2016-11-16 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SCN2A gene. The M1374K 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 and and the 1000 Genomes Project reports M1347K was observed in 1/170 (0.56%) of alleles from individuals of Sierre Lione background. The M1374K 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 alters a position conserved in mammals predicted to be within the extracellular loop between the S5 and S6 transmembrane segments of the third homologous domain. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV001063398 | SCV001228241 | likely benign | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2022-11-15 | criteria provided, single submitter | clinical testing |