Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003324350 | SCV004028609 | pathogenic | Familial hypokalemia-hypomagnesemia | 2023-07-28 | criteria provided, single submitter | clinical testing | Variant summary: SLC12A3 c.788_805dup18 (p.Ile263_Val268dup) results in an in-frame duplication that is predicted to duplicate six amino acids in the Amino acid permease/ SLC12A domain (IPR004841) of the encoded protein. The variant was absent in 251464 control chromosomes. c.788_805dup18 has been reported in the literature as a homozygous or compound heterozygous genotype in individuals affected with Familial Hypokalemia-Hypomagnesemia (Gitelman syndrome) (example, Fujimara_2019, Tajima_2002, Mori_2021). In these reports, it has also been variably annotated as c.805_806insATTGGCGTGGTCTCGGTC resulting in the identical amino acid change (p.Ile263_Val268dup) (Mori_2021 citing Tajima_2002). Additionally, the HGMD database lists a different variant, c.805_806ins18 (CI023563) resulting in a slightly different amino acid change [p.(Val268_Thr269insIleGlyValValSerVal)] while citing Tajima_2002 ascertained above. A closer review of the sequence indicates that these two variants may be identical. These data indicate that c.788_805dup18 (p.Ile263_Val268dup) is located in a critically important region and is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |