Submissions for variant NM_000891.3(KCNJ2):c.616G>A (p.Gly206Ser)

gnomAD frequency: 0.00011  dbSNP: rs141035459

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724926	SCV000332457	uncertain significance	not provided	2015-06-26	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000340562	SCV000539448	uncertain significance	not specified	2016-03-31	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 patient in 1 paper; ExAC: 1/10406 African
Labcorp Genetics (formerly Invitae), Labcorp	RCV000644781	SCV000766495	uncertain significance	Andersen Tawil syndrome; Short QT syndrome type 3	2023-12-19	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 206 of the KCNJ2 protein (p.Gly206Ser). This variant is present in population databases (rs141035459, gnomAD 0.008%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of KCNJ2-related conditions (PMID: 23631430). ClinVar contains an entry for this variant (Variation ID: 281601). 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 not expected to disrupt KCNJ2 protein function with a negative predictive value of 80%. 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	RCV002356365	SCV002654537	benign	Cardiovascular phenotype	2023-02-23	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics	RCV002503981	SCV002806823	uncertain significance	Andersen Tawil syndrome; Short QT syndrome type 3; Atrial fibrillation, familial, 9	2021-12-27	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000724926	SCV005198532	uncertain significance	not provided	2022-12-01	criteria provided, single submitter	clinical testing