Submissions for variant NM_172107.4(KCNQ2):c.1A>G (p.Met1Val)

dbSNP: rs118192185

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000421973	SCV000513366	pathogenic	not provided	2024-07-22	criteria provided, single submitter	clinical testing	Initiation codon variant in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Reported in patients with features consistent with KCNQ2-related epilepsy in published literature (PMID: 14985406, 25959266, 38814296); This variant is associated with the following publications: (PMID: 25982755, 27602407, 14985406, 19380078, 20437616, 25959266, 31440721, 38814296)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000552408	SCV000634056	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2023-12-14	criteria provided, single submitter	clinical testing	This sequence change affects the initiator methionine of the KCNQ2 mRNA. The next in-frame methionine is located at codon 174. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with benign familial neonatal seizures (PMID: 14985406, 25982755). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 21774). This variant disrupts the p.Arg144 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23934111, 25740509). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000421973	SCV000892665	likely pathogenic	not provided	2018-04-01	criteria provided, single submitter	clinical testing
GeneReviews	RCV000678067	SCV000041626	not provided	Seizures, benign familial neonatal, 1		no assertion provided	literature only	BFNE (benign familial neonatal epilepsy)