ClinVar Miner

Submissions for variant NM_003060.4(SLC22A5):c.1403C>A (p.Thr468Lys)

gnomAD frequency: 0.00004  dbSNP: rs386134221
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000635353 SCV000756758 likely pathogenic Renal carnitine transport defect 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 468 of the SLC22A5 protein (p.Thr468Lys). This variant is present in population databases (rs386134221, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SLC22A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 529852). 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 disrupts the p.Thr468 amino acid residue in SLC22A5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12210323, 15714519, 16652335). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Giacomini Lab, University of California, San Francisco RCV000635353 SCV002576699 uncertain significance Renal carnitine transport defect 2022-10-03 criteria provided, single submitter research
Natera, Inc. RCV002226477 SCV002078356 uncertain significance Decreased circulating carnitine concentration 2021-07-19 no assertion criteria provided clinical testing
Natera, Inc. RCV000635353 SCV002107478 uncertain significance Renal carnitine transport defect 2021-07-19 no assertion criteria provided clinical testing

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