Submissions for variant NM_003060.4(SLC22A5):c.706T>C (p.Cys236Arg)

gnomAD frequency: 0.00002  dbSNP: rs747050292

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000698273	SCV000826928	uncertain significance	Renal carnitine transport defect	2023-11-08	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 236 of the SLC22A5 protein (p.Cys236Arg). This variant is present in population databases (rs747050292, gnomAD 0.01%). This missense change has been observed in individual(s) with a positive newborn screening result for SLC22A5-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 575922). 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 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	RCV000698273	SCV002049548	uncertain significance	Renal carnitine transport defect	2021-01-25	criteria provided, single submitter	clinical testing	The SLC22A5 c.706T>C; p.Cys236Arg variant (rs747050292), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 575922). This variant is found in the Latino population with an allele frequency of 0.01% (5/34592 alleles) in the Genome Aggregation Database. The cysteine at codon 236 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.754). However, given the lack of clinical and functional data, the significance of the p.Cys236Arg variant is uncertain at this time.
Giacomini Lab, University of California, San Francisco	RCV000698273	SCV002576582	uncertain significance	Renal carnitine transport defect	2022-10-03	criteria provided, single submitter	research
Natera, Inc.	RCV002226487	SCV002078313	uncertain significance	Decreased circulating carnitine concentration	2019-11-11	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000698273	SCV002107436	uncertain significance	Renal carnitine transport defect	2019-11-11	no assertion criteria provided	clinical testing