ClinVar Miner

Submissions for variant NM_003060.4(SLC22A5):c.1373T>C (p.Val458Ala)

gnomAD frequency: 0.00007  dbSNP: rs753268767
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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 RCV001247135 SCV001420542 uncertain significance Renal carnitine transport defect 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 458 of the SLC22A5 protein (p.Val458Ala). This variant is present in population databases (rs753268767, gnomAD 0.009%). 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: 971368). 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. 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.
Baylor Genetics RCV001247135 SCV003836392 uncertain significance Renal carnitine transport defect 2022-03-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV004671299 SCV005171712 uncertain significance Inborn genetic diseases 2024-03-15 criteria provided, single submitter clinical testing The c.1373T>C (p.V458A) alteration is located in exon 8 (coding exon 8) of the SLC22A5 gene. This alteration results from a T to C substitution at nucleotide position 1373, causing the valine (V) at amino acid position 458 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV004762021 SCV005370345 uncertain significance not provided 2024-04-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV002226528 SCV002078355 uncertain significance Decreased circulating carnitine concentration 2020-05-01 no assertion criteria provided clinical testing
Natera, Inc. RCV001247135 SCV002107477 uncertain significance Renal carnitine transport defect 2020-05-01 no assertion criteria provided clinical testing

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