Submissions for variant NM_001161352.2(KCNMA1):c.3241G>A (p.Ala1081Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003087820	SCV003473586	uncertain significance	Generalized epilepsy-paroxysmal dyskinesia syndrome	2024-11-10	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 1023 of the KCNMA1 protein (p.Ala1023Thr). This variant is present in population databases (rs773135310, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with KCNMA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2160997). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt KCNMA1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV003456545	SCV004184057	uncertain significance	not provided	2023-11-01	criteria provided, single submitter	clinical testing	KCNMA1: PM2, PP2