Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000176314 | SCV000227948 | pathogenic | not provided | 2018-01-30 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV001095653 | SCV001251408 | likely pathogenic | Cognitive impairment with or without cerebellar ataxia | 2019-10-15 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001219444 | SCV001391383 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1323 of the SCN8A protein (p.Ala1323Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of developmental and epileptic encephalopathy (PMID: 29100083, 33201365; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 195688). 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 SCN8A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Institute of Human Genetics, |
RCV001253356 | SCV001429028 | likely pathogenic | Developmental and epileptic encephalopathy, 13 | 2018-12-03 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000176314 | SCV001769668 | pathogenic | not provided | 2023-06-21 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); The majority of missense variants in this gene are considered pathogenic; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be within the Intracellular loop between the S4 and S5 transmembrane segments of the third homologous domain; This variant is associated with the following publications: (PMID: 29100083, 32090326, 33201365, 35325842, 34979445) |
MGZ Medical Genetics Center | RCV001253356 | SCV002579567 | likely pathogenic | Developmental and epileptic encephalopathy, 13 | 2022-02-14 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002321698 | SCV002626319 | likely pathogenic | Inborn genetic diseases | 2018-01-29 | criteria provided, single submitter | clinical testing | The p.A1323T variant (also known as c.3967G>A), located in coding exon 21 of the SCN8A gene, results from a G to A substitution at nucleotide position 3967. The alanine at codon 1323 is replaced by threonine, an amino acid with similar properties. This variant has been determined to be the result of a de novo mutation or germline mosaicism in one individual with focal epilepsy (Ambry internal data). An alternate amino acid substitution at this position, p.A1323S, has been reported as de novo in an individual with early infantile epileptic encephalopathy; however, clinical details were limited (Trump N et al. J. Med. Genet., 2016 May;53:310-7). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Génétique des Maladies du Développement, |
RCV001253356 | SCV001943318 | pathogenic | Developmental and epileptic encephalopathy, 13 | no assertion criteria provided | clinical testing |