Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188998 | SCV000242629 | likely pathogenic | not provided | 2023-05-24 | criteria provided, single submitter | clinical testing | Identified in at least one individual in a cohort of individuals with epilepsy and neurodevelopmental disorders in published literature (Lindy et al., 2018); This substitution is predicted to be within the transmembrane segment S6 of the fourth homologous domain; The majority of missense variants in this gene are considered pathogenic (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29655203) |
Invitae | RCV001065456 | SCV001230414 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 1764 of the SCN1A protein (p.Phe1764Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant developmental and epileptic encephalopathy (PMID: 29655203; Invitae). ClinVar contains an entry for this variant (Variation ID: 206863). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Center for Personalized Medicine, |
RCV003156083 | SCV003845321 | likely pathogenic | See cases | 2022-12-21 | criteria provided, single submitter | clinical testing |