Submissions for variant NM_172107.4(KCNQ2):c.1600C>T (p.Pro534Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003590927	SCV004278858	uncertain significance	Early infantile epileptic encephalopathy with suppression bursts	2022-12-20	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 534 of the KCNQ2 protein (p.Pro534Ser). This variant is present in population databases (rs760066570, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. 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 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.
Ambry Genetics	RCV004985404	SCV005608362	uncertain significance	Inborn genetic diseases	2024-08-05	criteria provided, single submitter	clinical testing	The c.1600C>T (p.P534S) alteration is located in exon 14 (coding exon 14) of the KCNQ2 gene. This alteration results from a C to T substitution at nucleotide position 1600, causing the proline (P) at amino acid position 534 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.