ClinVar Miner

Submissions for variant NM_000338.3(SLC12A1):c.1103A>G (p.Glu368Gly)

gnomAD frequency: 0.00001  dbSNP: rs1567314296
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001909397 SCV002187270 uncertain significance not provided 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 368 of the SLC12A1 protein (p.Glu368Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with Bartter syndrome (PMID: 19096086). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Mendelics RCV002246590 SCV002519745 pathogenic Bartter disease type 1 2022-05-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV004042767 SCV004951036 likely pathogenic Inborn genetic diseases 2024-02-29 criteria provided, single submitter clinical testing The c.1103A>G (p.E368G) alteration is located in exon 9 (coding exon 8) of the SLC12A1 gene. This alteration results from a A to G substitution at nucleotide position 1103, causing the glutamic acid (E) at amino acid position 368 to be replaced by a glycine (G). Based on data from gnomAD, the G allele has an overall frequency of <0.001% (1/250968) total alleles studied. The highest observed frequency was 0.003% (1/34588) of Latino alleles. This variant was detected homozygous in one individual diagnosed with neonatal Bartter syndrome and was detected in trans with a SLC12A1 variant in another individual with polyuria, hypokalemia, hyponatremia, and low birth weight at birth (Brochard, 2009; D'Angelantonio, 2022) This amino acid position is highly conserved in available vertebrate species. In a functional study testing SL12A1 localization and expression, this variant resulted in abnormal results (Shaukat, 2021). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002246590 SCV005630700 likely pathogenic Bartter disease type 1 2024-02-08 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.