Submissions for variant NM_004519.4(KCNQ3):c.569G>A (p.Arg190Gln)

dbSNP: rs796052674

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187965	SCV000241568	uncertain significance	not provided	2019-01-29	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV001852467	SCV002115274	uncertain significance	Benign neonatal seizures	2023-07-10	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 190 of the KCNQ3 protein (p.Arg190Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of KCNQ3-related conditions (PMID: 33004838; Invitae). ClinVar contains an entry for this variant (Variation ID: 205960). 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 KCNQ3 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	RCV002516995	SCV003550013	uncertain significance	Inborn genetic diseases	2021-01-27	criteria provided, single submitter	clinical testing	The c.569G>A (p.R190Q) alteration is located in exon 3 (coding exon 3) of the KCNQ3 gene. This alteration results from a G to A substitution at nucleotide position 569, causing the arginine (R) at amino acid position 190 to be replaced by a glutamine (Q). The p.R190Q alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003955124	SCV004771453	uncertain significance	KCNQ3-related condition	2023-12-11	criteria provided, single submitter	clinical testing	The KCNQ3 c.569G>A variant is predicted to result in the amino acid substitution p.Arg190Gln. This variant has been reported as arising de novo in an individual with a neurodevelopmental disorder (Table S5, Wang et al. 2020. PubMed ID: 33004838). This variant has not been reported in a large population database, indicating this variant is rare. Although we suspect this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.