Submissions for variant NM_003060.4(SLC22A5):c.1645C>T (p.Pro549Ser)

gnomAD frequency: 0.02345  dbSNP: rs11568525

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000128068	SCV000171659	benign	not specified	2014-05-16	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina	RCV000022390	SCV000452741	likely benign	Renal carnitine transport defect	2017-04-28	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000022390	SCV000632541	benign	Renal carnitine transport defect	2025-02-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000022390	SCV000886115	benign	Renal carnitine transport defect	2023-10-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000128068	SCV000920210	benign	not specified	2018-11-12	criteria provided, single submitter	clinical testing	Variant summary: SLC22A5 c.1645C>T (p.Pro549Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0072 in 277216 control chromosomes in the gnomAD database, including 83 homozygotes. The observed variant frequency is approximately 2-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in SLC22A5 causing Systemic Primary Carnitine Deficiency phenotype (0.0046), strongly suggesting that the variant is benign. c.1645C>T has been reported in the literature in individuals affected with Systemic Primary Carnitine Deficiency . These report(s) do not provide unequivocal conclusions about association of the variant with Systemic Primary Carnitine Deficiency . Multiple functional studies, Amat di San Filippo_2008, Frigeni_2017, Urban_2006, found the variant to act comparable to wild type function. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.
Genome-Nilou Lab	RCV000022390	SCV002055883	benign	Renal carnitine transport defect	2021-07-15	criteria provided, single submitter	clinical testing
Giacomini Lab, University of California, San Francisco	RCV000022390	SCV002576621	likely benign	Renal carnitine transport defect	2022-10-03	criteria provided, single submitter	research
Breakthrough Genomics, Breakthrough Genomics	RCV004704814	SCV005226528	likely benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV000022390	SCV001452787	benign	Renal carnitine transport defect	2020-09-16	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003924854	SCV004746117	benign	SLC22A5-related disorder	2020-03-25	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).