ClinVar Miner

Submissions for variant NM_001365088.1(SLC12A6):c.1369A>T (p.Ile457Phe)

gnomAD frequency: 0.00006  dbSNP: rs751420584
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002537879 SCV003475603 uncertain significance not provided 2024-03-21 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 457 of the SLC12A6 protein (p.Ile457Phe). This variant is present in population databases (rs751420584, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SLC12A6-related conditions. ClinVar contains an entry for this variant (Variation ID: 991876). 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 not expected to disrupt SLC12A6 protein function with a negative predictive value of 80%. 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.
Natera, Inc. RCV001280159 SCV001467316 uncertain significance Agenesis of the corpus callosum with peripheral neuropathy 2020-04-18 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003898266 SCV004727688 uncertain significance SLC12A6-related disorder 2023-12-05 no assertion criteria provided clinical testing The SLC12A6 c.1369A>T variant is predicted to result in the amino acid substitution p.Ile457Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0070% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.