Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Bioinformatics, |
RCV000180879 | SCV000221848 | pathogenic | Severe myoclonic epilepsy in infancy | 2014-12-20 | criteria provided, single submitter | research | |
Rady Children's Institute for Genomic Medicine, |
RCV000180879 | SCV000996091 | pathogenic | Severe myoclonic epilepsy in infancy | 2017-12-14 | criteria provided, single submitter | clinical testing | This variant has been previously reported as disease causing in a patient with severe myoclonic epilepsy in infancy and in the patient's sibling with generalized epilepsy with febrile seizures (PMID: 12919402) and in an individual with Dravet syndrome (PMID: 26096185). The c.5555T>C (p.Met1852Thr) variant is absent from population databases, thus is presumed to be rare. Functional studies show that this change is a loss of function variant, specifically affecting cellular trafficking (PMID: 17928445). In silico algorithms predict this change to be deleterious. Based on the overall evidence the c.5555T>C (p.Met1852Thr) variant is classified as pathogenic. |
Invitae | RCV001854247 | SCV002223528 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-02-21 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1852 of the SCN1A protein (p.Met1852Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SCN1A-related conditions (PMID: 12919402, 26096185, 31019026). In at least one individual the variant was observed to be de novo. This variant is also known as p.Met1841Thr. ClinVar contains an entry for this variant (Variation ID: 68664). 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. For these reasons, this variant has been classified as Pathogenic. |
Uni |
RCV000059544 | SCV000091076 | not provided | Generalized epilepsy with febrile seizures plus, type 1 | no assertion provided | not provided |