Submissions for variant NM_003060.4(SLC22A5):c.391G>A (p.Glu131Lys)

gnomAD frequency: 0.00001  dbSNP: rs1321705165

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001938987	SCV002200628	uncertain significance	Renal carnitine transport defect	2022-08-09	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 131 of the SLC22A5 protein (p.Glu131Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1429538). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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	RCV001938987	SCV002576670	uncertain significance	Renal carnitine transport defect	2022-10-03	criteria provided, single submitter	research
Fulgent Genetics, Fulgent Genetics	RCV001938987	SCV002816639	uncertain significance	Renal carnitine transport defect	2021-11-13	criteria provided, single submitter	clinical testing
GeneDx	RCV003107900	SCV003761757	uncertain significance	not provided	2023-01-25	criteria provided, single submitter	clinical testing	Described as a non deleterious variant, with functional studies of carnitine uptake by OCNT2 in transfected cells showing no significant difference compared to wildtype (Rodin M et al., 2020); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: Rdin2020[DegreeProject])
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV001938987	SCV005016525	uncertain significance	Renal carnitine transport defect	2024-03-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003107900	SCV005075097	uncertain significance	not provided	2024-06-01	criteria provided, single submitter	clinical testing	SLC22A5: PM2, PP3
Breakthrough Genomics, Breakthrough Genomics	RCV003107900	SCV005188588	uncertain significance	not provided		criteria provided, single submitter	not provided