Submissions for variant NM_003060.4(SLC22A5):c.770G>A (p.Arg257Gln)

gnomAD frequency: 0.00006  dbSNP: rs148989838

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000799874	SCV000939557	uncertain significance	Renal carnitine transport defect	2022-09-13	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 257 of the SLC22A5 protein (p.Arg257Gln). This variant is present in population databases (rs148989838, gnomAD 0.01%). 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: 645726). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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	RCV000799874	SCV002576729	uncertain significance	Renal carnitine transport defect	2022-10-03	criteria provided, single submitter	research
Natera, Inc.	RCV002226492	SCV002078316	uncertain significance	Decreased circulating carnitine concentration	2021-01-04	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000799874	SCV002107440	uncertain significance	Renal carnitine transport defect	2021-01-04	no assertion criteria provided	clinical testing