Submissions for variant NM_003060.4(SLC22A5):c.368T>G (p.Val123Gly)

gnomAD frequency: 0.00002  dbSNP: rs748605096

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001244235	SCV001417441	uncertain significance	Renal carnitine transport defect	2022-03-16	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 123 of the SLC22A5 protein (p.Val123Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with abnormal newborn screening for carnitine deficiency (PMID: 20574985). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 968989). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects 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.
Giacomini Lab, University of California, San Francisco	RCV001244235	SCV002576719	uncertain significance	Renal carnitine transport defect	2022-10-03	criteria provided, single submitter	research
Natera, Inc.	RCV002226525	SCV002078300	uncertain significance	Decreased circulating carnitine concentration	2020-05-15	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001244235	SCV002107423	uncertain significance	Renal carnitine transport defect	2020-05-15	no assertion criteria provided	clinical testing