Submissions for variant NM_172107.4(KCNQ2):c.1504G>A (p.Ala502Thr)

gnomAD frequency: 0.00001  dbSNP: rs540103798

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001060721	SCV001225425	uncertain significance	Early infantile epileptic encephalopathy with suppression bursts	2024-10-24	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 502 of the KCNQ2 protein (p.Ala502Thr). This variant is present in population databases (rs540103798, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 855445). 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) has been performed 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 KCNQ2 protein function. 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	RCV004597957	SCV005092228	uncertain significance	not provided	2024-07-01	criteria provided, single submitter	clinical testing