Submissions for variant NM_003060.4(SLC22A5):c.118G>A (p.Val40Met)

gnomAD frequency: 0.00001  dbSNP: rs148657753

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001157362	SCV001318928	uncertain significance	Renal carnitine transport defect	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001157362	SCV001388729	uncertain significance	Renal carnitine transport defect	2021-11-02	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 40 of the SLC22A5 protein (p.Val40Met). This variant is present in population databases (rs148657753, gnomAD 0.002%). 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: 907482). 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.
Genome-Nilou Lab	RCV001157362	SCV002055839	uncertain significance	Renal carnitine transport defect	2021-07-15	criteria provided, single submitter	clinical testing
GenomeConnect - Invitae Patient Insights Network	RCV001157362	SCV004228778	not provided	Renal carnitine transport defect		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 12-20-2020 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.