Submissions for variant NM_003060.4(SLC22A5):c.77G>A (p.Ser26Asn)

gnomAD frequency: 0.00001  dbSNP: rs772578415

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000439652	SCV000515967	pathogenic	not provided	2015-03-07	criteria provided, single submitter	clinical testing	The S26N missense variant has been reported previouslyin association with PCD in an asymptomatic woman who was compound heterozygous for the S26N variant and a second SLC22A5 variant and who had an infant with positive newborn screening (Rose et al., 2012). Functional analysis of the S26N substitution found that it is associated with significantly reduced carnitine transport (Rose et al., 2012). Therefore, we interpret S26N as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001237032	SCV001409779	likely pathogenic	Renal carnitine transport defect	2024-11-11	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 26 of the SLC22A5 protein (p.Ser26Asn). This variant is present in population databases (rs772578415, gnomAD 0.003%). This missense change has been observed in individual(s) with primary carnitine deficiency (PMID: 21922592). ClinVar contains an entry for this variant (Variation ID: 379259). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SLC22A5 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SLC22A5 function (PMID: 21922592, 28841266, 36343260). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Genome-Nilou Lab	RCV001237032	SCV002055788	likely pathogenic	Renal carnitine transport defect	2021-07-15	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001237032	SCV004203578	likely pathogenic	Renal carnitine transport defect	2023-03-23	criteria provided, single submitter	clinical testing
Giacomini Lab, University of California, San Francisco	RCV001237032	SCV002576640	uncertain significance	Renal carnitine transport defect	2022-10-03	flagged submission	research