Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
RCV001195896 | SCV001366320 | pathogenic | Migraine, familial hemiplegic, 3 | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM1,PM2,PP2,PP3. |
Labcorp Genetics |
RCV001863098 | SCV002219908 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2021-10-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SCN1A protein function. ClinVar contains an entry for this variant (Variation ID: 930321). This missense change has been observed in individual(s) with Dravet syndrome (PMID: 18930999). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with histidine at codon 1781 of the SCN1A protein (p.Tyr1781His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. |