Submissions for variant NM_001126108.2(SLC12A3):c.2213T>G (p.Leu738Arg)

dbSNP: rs2144733006

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001886034	SCV002139872	pathogenic	not provided	2023-07-25	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 1376627). This missense change has been observed in individual(s) with Gitelman syndrome (PMID: 9734597, 17159356). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 738 of the SLC12A3 protein (p.Leu738Arg). For these reasons, this variant has been classified as Pathogenic. 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 SLC12A3 protein function.
European Hospital Georges Pompidou Genetics Department, Assistance Publique - Hôpitaux de Paris AP-HP	RCV002243478	SCV002513816	likely pathogenic	Familial hypokalemia-hypomagnesemia	2022-04-27	criteria provided, single submitter	clinical testing	ACMG criteria used:PS4, PM1, PM2, PM3, PP5
Fulgent Genetics, Fulgent Genetics	RCV002243478	SCV002787963	likely pathogenic	Familial hypokalemia-hypomagnesemia	2021-11-09	criteria provided, single submitter	clinical testing