Submissions for variant NM_003060.4(SLC22A5):c.122T>G (p.Phe41Cys)

gnomAD frequency: 0.00001  dbSNP: rs1335556134

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000697989	SCV000826627	uncertain significance	Renal carnitine transport defect	2022-09-23	criteria provided, single submitter	clinical testing	This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 41 of the SLC22A5 protein (p.Phe41Cys). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 575694). 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. 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	RCV000697989	SCV002576653	uncertain significance	Renal carnitine transport defect	2022-10-03	criteria provided, single submitter	research
Natera, Inc.	RCV002226485	SCV002075433	uncertain significance	Decreased circulating carnitine concentration	2021-05-13	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000697989	SCV002107437	uncertain significance	Renal carnitine transport defect	2021-05-13	no assertion criteria provided	clinical testing