Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000255423 | SCV000322055 | pathogenic | not provided | 2023-01-03 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that N995S results in a gain-of-function with markedly increased macroscopic potassium current (Li et al., 2018; Moldenhauer et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as N1053S using alternate nomenclature; This variant is associated with the following publications: (PMID: 32132200, 32655623, 26195193, 29330545, 30525188, 31152168, 31851553, 32633875, 33043086, 33767182) |
Invitae | RCV000504575 | SCV000830549 | pathogenic | Generalized epilepsy-paroxysmal dyskinesia syndrome | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 995 of the KCNMA1 protein (p.Asn995Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with epilepsy and/or paroxysomal dyskinesia (PMID: 26195193, 29330545; Invitae). In at least one individual the variant was observed to be de novo. This variant is also known as c.3158A>G (p.Asn1053Ser). ClinVar contains an entry for this variant (Variation ID: 265313). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KCNMA1 protein function. Experimental studies have shown that this missense change affects KCNMA1 function (PMID: 29330545). For these reasons, this variant has been classified as Pathogenic. |
Undiagnosed Diseases Network, |
RCV000504575 | SCV000863433 | pathogenic | Generalized epilepsy-paroxysmal dyskinesia syndrome | 2018-10-05 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000255423 | SCV002497043 | pathogenic | not provided | 2022-02-01 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000504575 | SCV000598623 | pathogenic | Generalized epilepsy-paroxysmal dyskinesia syndrome | 2017-08-30 | no assertion criteria provided | literature only | |
Pediatric Genetics Clinic, |
RCV000504575 | SCV001712187 | likely pathogenic | Generalized epilepsy-paroxysmal dyskinesia syndrome | 2021-05-13 | no assertion criteria provided | clinical testing | |
Center of Excellence for Medical Genomics, |
RCV000504575 | SCV002570056 | likely pathogenic | Generalized epilepsy-paroxysmal dyskinesia syndrome | 2002-09-08 | no assertion criteria provided | research |