ClinVar Miner

Submissions for variant NM_003060.4(SLC22A5):c.1234A>C (p.Ser412Arg)

dbSNP: rs1057518364
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414398 SCV000491934 uncertain significance not specified 2016-11-14 criteria provided, single submitter clinical testing The S412R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S412R variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S412R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001068837 SCV001233970 uncertain significance Renal carnitine transport defect 2025-01-21 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 412 of the SLC22A5 protein (p.Ser412Arg). This variant is not present in population databases (gnomAD no frequency). 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: 373347). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SLC22A5 protein function with a positive predictive value of 95%. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001257252 SCV001433794 uncertain significance not provided 2018-03-20 criteria provided, single submitter clinical testing The SLC22A5 c.1234A>C; p.Ser412Arg (rs1057518364) variant is not described in the medical literature but is reported as a variant of uncertain significance by one laboratory in ClinVar (Variation ID: 373347). It is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The serine at codon 412 is weakly conserved and computational algorithms (SIFT, PolyPhen2) predict that this variant is tolerated. Due to limited information regarding this variant, its clinical significance cannot be determined with certainty.
Genome-Nilou Lab RCV001068837 SCV002055859 uncertain significance Renal carnitine transport defect 2021-07-15 criteria provided, single submitter clinical testing

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