ClinVar Miner

Submissions for variant NM_003060.4(SLC22A5):c.43G>T (p.Gly15Trp)

gnomAD frequency: 0.00010  dbSNP: rs267607052
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000006798 SCV000220653 likely pathogenic Renal carnitine transport defect 2014-08-28 criteria provided, single submitter literature only
GeneDx RCV000186150 SCV000239176 pathogenic not provided 2020-10-01 criteria provided, single submitter clinical testing 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: 21922592, 26828774, 28841266, 20027113, 20574985, 21126579, 28711408)
Labcorp Genetics (formerly Invitae), Labcorp RCV000006798 SCV000632552 pathogenic Renal carnitine transport defect 2025-01-11 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 15 of the SLC22A5 protein (p.Gly15Trp). This variant is present in population databases (rs267607052, gnomAD 0.08%). This missense change has been observed in individual(s) with primary carnitine deficiency (PMID: 20027113, 20574985, 21922592). ClinVar contains an entry for this variant (Variation ID: 6429). 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%. Experimental studies have shown that this missense change affects SLC22A5 function (PMID: 21922592). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000006798 SCV000698150 pathogenic Renal carnitine transport defect 2017-01-06 criteria provided, single submitter clinical testing Variant summary: The SLC22A5 c.43G>T (p.Gly15Trp) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 12/116676 control chromosomes at a frequency of 0.0001028, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC22A5 variant (0.0045644). This variant has been reported in many patients both as homozygotes and compound heterozygote. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. Taken together, this variant is classified as pathogenic.
Genome-Nilou Lab RCV000006798 SCV001821587 pathogenic Renal carnitine transport defect 2021-07-22 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000006798 SCV002020643 pathogenic Renal carnitine transport defect 2022-10-18 criteria provided, single submitter clinical testing
Giacomini Lab, University of California, San Francisco RCV000006798 SCV002576650 pathogenic Renal carnitine transport defect 2022-10-03 criteria provided, single submitter research
Fulgent Genetics, Fulgent Genetics RCV000006798 SCV002792002 likely pathogenic Renal carnitine transport defect 2022-01-14 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000006798 SCV004048048 pathogenic Renal carnitine transport defect 2023-07-22 criteria provided, single submitter clinical testing The observed missense c.43G>Tp.Gly15Trp variant in SLC22A5 gene has been reported previously in homozygous and compound heterozygous states in multiple individuals affected with primary carnitine deficiency El-Hattab et al., 2010; Li et al., 2010; Rose et al., 2012. Experimental studies have shown that this missense change affects SLC22A5 function Rose et al., 2012. The p.Gly15Trp variant is present with allele frequency of 0.01% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Likely Pathogenic/ Pathogenic multiple submissions. Multiple lines of computational evidence Polyphen - Probably Damaging, SIFT - Damaging and MutationTaster - Disease causing predict a damaging effect on protein structure and function for this variant. The reference amino acid of p.Gly15Trp in SLC22A5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Gly at position 15 is changed to a Trp changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Pathogenic. In absence of another reportable variant in SLC22A5 gene, the molecular diagnosis is not confirmed.
Baylor Genetics RCV000006798 SCV004201275 pathogenic Renal carnitine transport defect 2024-03-07 criteria provided, single submitter clinical testing
OMIM RCV000006798 SCV000026994 pathogenic Renal carnitine transport defect 2010-01-01 no assertion criteria provided literature only
Natera, Inc. RCV000006798 SCV001458678 pathogenic Renal carnitine transport defect 2020-09-16 no assertion criteria provided clinical testing

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