Submissions for variant NM_172107.4(KCNQ2):c.2102_2104del (p.Phe701del)

dbSNP: rs758334927

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187946	SCV000241549	uncertain significance	not specified	2013-11-04	criteria provided, single submitter	clinical testing	c.2102_2104delTCT: p.Phe701del in exon 17 in the KCNQ2 gene (NM_172107.2). The normal sequence with the bases that are deleted in braces is: AACT{TCT}CGGC. The c.2102_2104delTCT variant in the KCNQ2 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. This variant is an in-frame deletion of the Phenylalanine 170, denoted p.Phe710del, which is a residue that is not well conserved across species. The c.2102_2104delTCT variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Other in-frame deletions in the KCNQ2 gene have been reported in association with epilepsy. We interpret c.2102_2104delTCT as a variant of unknown significance. The variant is found in KCNQ2 panel(s).
Invitae	RCV000545156	SCV000634058	uncertain significance	Early infantile epileptic encephalopathy with suppression bursts	2023-06-18	criteria provided, single submitter	clinical testing	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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on KCNQ2 function (PMID: 35104249). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 205944). This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. This variant is present in population databases (rs758334927, gnomAD 0.002%). This variant, c.2102_2104del, results in the deletion of 1 amino acid(s) of the KCNQ2 protein (p.Phe701del), but otherwise preserves the integrity of the reading frame.
Mayo Clinic Laboratories, Mayo Clinic	RCV000660450	SCV000782543	uncertain significance	Seizures, benign familial neonatal, 1; Developmental and epileptic encephalopathy, 7	2016-12-28	criteria provided, single submitter	clinical testing
Channelopathy-Associated Epilepsy Research Center	RCV003315328	SCV004015036	not provided	Complex neurodevelopmental disorder		no assertion provided	literature only