ClinVar Miner

Submissions for variant NM_003060.4(SLC22A5):c.1043T>C (p.Ile348Thr)

gnomAD frequency: 0.00016  dbSNP: rs150544263
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000022361 SCV000756749 uncertain significance Renal carnitine transport defect 2022-10-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 348 of the SLC22A5 protein (p.Ile348Thr). This variant is present in population databases (rs150544263, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of primary carnitine deficiency (PMID: 17486650, 28841266). ClinVar contains an entry for this variant (Variation ID: 25407). 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 not expected to disrupt SLC22A5 protein function. Experimental studies have shown that this missense change does not substantially affect SLC22A5 function (PMID: 28841266). 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.
Fulgent Genetics, Fulgent Genetics RCV000022361 SCV000895659 uncertain significance Renal carnitine transport defect 2018-10-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000022361 SCV001317233 uncertain significance Renal carnitine transport defect 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx RCV001552646 SCV001773371 likely benign not provided 2021-05-21 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28841266)
Genome-Nilou Lab RCV000022361 SCV002055762 uncertain significance Renal carnitine transport defect 2021-07-15 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000022361 SCV004237312 uncertain significance Renal carnitine transport defect 2023-09-17 criteria provided, single submitter clinical testing
Clinical Genomics Laboratory, Stanford Medicine RCV000022361 SCV004804530 uncertain significance Renal carnitine transport defect 2021-06-04 criteria provided, single submitter clinical testing • The p.Ile348Thr variant in the SLC22A5 gene has been previously reported in 1 individual referred for possible carnitine deficiency without a second variant identified (Frigeni et al., 2017). • The p.Ile348Thr variant has also been identified in 10/19,954 East Asian chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. • Computational tools predict that this variant does not impact protein function; however, the accuracy of in silico algorithms is limited. • These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Ile348Thr variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PM2]
Mayo Clinic Laboratories, Mayo Clinic RCV001552646 SCV005411869 uncertain significance not provided 2024-09-13 criteria provided, single submitter clinical testing
Natera, Inc. RCV000022361 SCV001458335 uncertain significance Renal carnitine transport defect 2020-01-02 no assertion criteria provided clinical testing

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