Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000189208 | SCV000242840 | likely pathogenic | not provided | 2016-09-30 | criteria provided, single submitter | clinical testing | An apparently de novo variant that is likely pathogenic has been identified in the SCN2A gene. The Y428C 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 Y428C 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 conserved position predicted to be within the intracellular loop between the S6 transmembrane segment of the first homologous domain and the S1 transmembrane segment of the second homologous domain. In silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, targeted parental test results indicate this variant is apparently de novo. Therefore, we now interpret Y428C as a likely pathogenic variant. |
| Genome |
RCV001265320 | SCV001443437 | likely pathogenic | Complex neurodevelopmental disorder | 2018-11-30 | no assertion criteria provided | provider interpretation | Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-11-30 and interpreted as Likely Pathogenic. Variant was initially reported on 2016-10-10 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar. |