Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
TIDEX, |
RCV000655959 | SCV000586851 | likely pathogenic | atypical cerebral palsy | criteria provided, single submitter | research | ||
Invitae | RCV001856998 | SCV002259207 | likely pathogenic | not provided | 2022-08-16 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 431726). This missense change has been observed in individual(s) with clinical features of SCN3A-related conditions (PMID: 30542205; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 209 of the SCN3A protein (p.Leu209Pro). |
3billion | RCV002250643 | SCV002521704 | likely pathogenic | Developmental and epileptic encephalopathy, 62 | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.97; 3Cnet: 0.94). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with SCN3A related disorder (ClinVar ID: VCV000431726 / PMID: 30542205). The variant has been previously reported as de novo in a similarly affected individual (PMID: 30542205). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |