Submissions for variant NM_001126108.2(SLC12A3):c.1568-1G>A

gnomAD frequency: 0.00001  dbSNP: rs199511487

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001927180	SCV002157982	pathogenic	not provided	2022-04-14	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is also known as c.1569-1G>A. Disruption of this splice site has been observed in individuals with Gitelman syndrome (PMID: 17654016). This variant is present in population databases (rs199511487, gnomAD 0.004%). This sequence change affects an acceptor splice site in intron 12 of the SLC12A3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC12A3 are known to be pathogenic (PMID: 20848653, 22009145, 25841442).
European Hospital Georges Pompidou Genetics Department, Assistance Publique - Hôpitaux de Paris AP-HP	RCV002243480	SCV002513835	pathogenic	Familial hypokalemia-hypomagnesemia	2022-04-27	criteria provided, single submitter	clinical testing	ACMG criteria used:PVS1 PM1 PM2 PM3 PP5