Submissions for variant NM_172107.4(KCNQ2):c.1955C>T (p.Pro652Leu)

dbSNP: rs770730662

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187955	SCV000241558	likely benign	not provided	2019-08-05	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000686537	SCV000814058	uncertain significance	Early infantile epileptic encephalopathy with suppression bursts	2024-08-30	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 652 of the KCNQ2 protein (p.Pro652Leu). This variant is present in population databases (rs770730662, 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: 205951). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
New York Genome Center	RCV001838986	SCV002099171	uncertain significance	Developmental and epileptic encephalopathy, 7	2021-05-14	criteria provided, single submitter	clinical testing	The inherited missense heterozygous variant c.1901C>T, p.Pro634Leu identified in KCNQ2 has not been reported in the literature. This variant has been reported as heterozygous in six individuals in the gnomAD v3.1 database, indicating this is a rare allele. In silico tools predict conflicting interpretation of pathogenicity. Based on the available evidence, the variant c.1901C>T, p.Pro634Leu in the KCNQ2 gene is classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002415807	SCV002722056	uncertain significance	Inborn genetic diseases	2023-09-29	criteria provided, single submitter	clinical testing	The c.1955C>T (p.P652L) alteration is located in exon 17 (coding exon 17) of the KCNQ2 gene. This alteration results from a C to T substitution at nucleotide position 1955, causing the proline (P) at amino acid position 652 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV000187955	SCV004150914	uncertain significance	not provided	2022-11-01	criteria provided, single submitter	clinical testing	KCNQ2: PM2:Supporting, PP2