Submissions for variant NM_001126108.2(SLC12A3):c.1850A>G (p.Gln617Arg)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004689521	SCV005185741	likely pathogenic	Familial hypokalemia-hypomagnesemia	2024-05-15	criteria provided, single submitter	clinical testing	Variant summary: SLC12A3 c.1850A>G (p.Gln617Arg) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.1850A>G has been reported in the literature in individuals affected with Familial Hypokalemia-Hypomagnesemia. These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 63% of normal activity. The following publications have been ascertained in the context of this evaluation (PMID: 34860177, 35628451, 28700713, 31398183). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.