ClinVar Miner

Submissions for variant NM_003060.4(SLC22A5):c.728A>C (p.Tyr243Ser)

gnomAD frequency: 0.00009  dbSNP: rs1321621475
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001036928 SCV001200317 likely pathogenic Renal carnitine transport defect 2024-01-05 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 243 of the SLC22A5 protein (p.Tyr243Ser). This variant is present in population databases (no rsID available, gnomAD 0.009%). This missense change has been observed in individual(s) with clinical features of primary carnitine deficiency (Invitae). ClinVar contains an entry for this variant (Variation ID: 835927). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SLC22A5 function (PMID: 36343260). 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 RCV001036928 SCV002576649 uncertain significance Renal carnitine transport defect 2022-10-03 criteria provided, single submitter research
Ambry Genetics RCV002552468 SCV003751910 uncertain significance Inborn genetic diseases 2021-07-08 criteria provided, single submitter clinical testing The c.728A>C (p.Y243S) alteration is located in exon 4 (coding exon 4) of the SLC22A5 gene. This alteration results from a A to C substitution at nucleotide position 728, causing the tyrosine (Y) at amino acid position 243 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV003160220 SCV003915096 likely pathogenic not provided 2023-03-31 criteria provided, single submitter clinical testing Functional analysis found this variant is associated with significantly impaired carnitine transport (Koleske ML et al., 2022); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 36343260)
Natera, Inc. RCV002226508 SCV002078314 uncertain significance Decreased circulating carnitine concentration 2021-01-19 no assertion criteria provided clinical testing
Natera, Inc. RCV001036928 SCV002107438 uncertain significance Renal carnitine transport defect 2021-01-19 no assertion criteria provided clinical testing

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