Submissions for variant NM_003060.4(SLC22A5):c.797C>T (p.Pro266Leu)

dbSNP: rs538372785

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001050052	SCV001214140	pathogenic	Renal carnitine transport defect	2024-12-24	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 266 of the SLC22A5 protein (p.Pro266Leu). This variant is present in population databases (rs538372785, gnomAD 0.05%). This missense change has been observed in individual(s) with primary carnitine deficiency (PMID: 30863740, 31364285). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 846688). 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) has been performed 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. This variant disrupts the p.Pro266 amino acid residue in SLC22A5. Other variant(s) that disrupt this residue have been observed in individuals with SLC22A5-related conditions (internal data), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV001050052	SCV004201277	pathogenic	Renal carnitine transport defect	2024-03-12	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001050052	SCV005417727	pathogenic	Renal carnitine transport defect		criteria provided, single submitter	clinical testing	PM2_Supporting+PM3_VeryStrong+PP4
Fulgent Genetics, Fulgent Genetics	RCV001050052	SCV005669214	likely pathogenic	Renal carnitine transport defect	2024-05-21	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV002226512	SCV002078320	pathogenic	Decreased circulating carnitine concentration	2020-11-04	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001050052	SCV002107443	pathogenic	Renal carnitine transport defect	2020-11-04	no assertion criteria provided	clinical testing
Giacomini Lab, University of California, San Francisco	RCV001050052	SCV002576657	uncertain significance	Renal carnitine transport defect	2022-10-03	flagged submission	research