ClinVar Miner

Submissions for variant NM_003060.4(SLC22A5):c.1138G>A (p.Ala380Thr)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Giacomini Lab, University of California, San Francisco RCV002286645 SCV002576642 uncertain significance Renal carnitine transport defect 2022-10-03 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV002286645 SCV003019428 likely pathogenic Renal carnitine transport defect 2022-07-22 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with SLC22A5-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ala380 amino acid residue in SLC22A5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23520115, 33181153, 33757571). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 expected to disrupt SLC22A5 protein function. This variant is present in population databases (rs781417085, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 380 of the SLC22A5 protein (p.Ala380Thr).

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.