Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000554108 | SCV000632559 | pathogenic | Renal carnitine transport defect | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 202 of the SLC22A5 protein (p.Leu202Pro). This variant is present in population databases (rs142447950, gnomAD 0.07%). This missense change has been observed in individual(s) with clinical features of primary carnitine deficiency (Invitae). 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: 460410). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV000554108 | SCV000895658 | uncertain significance | Renal carnitine transport defect | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000554108 | SCV002055849 | uncertain significance | Renal carnitine transport defect | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Giacomini Lab, |
RCV000554108 | SCV002576713 | uncertain significance | Renal carnitine transport defect | 2022-10-03 | criteria provided, single submitter | research | |
Mayo Clinic Laboratories, |
RCV003480672 | SCV004227123 | uncertain significance | not provided | 2023-02-23 | criteria provided, single submitter | clinical testing | PP3 |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004782429 | SCV005395156 | uncertain significance | not specified | 2024-09-09 | criteria provided, single submitter | clinical testing | Variant summary: SLC22A5 c.605T>C (p.Leu202Pro) results in a non-conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 251492 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in SLC22A5 causing Systemic Primary Carnitine Deficiency (0.00014 vs 0.0046), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.605T>C in individuals affected with Systemic Primary Carnitine Deficiency has been reported in the literature. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in >50%-90% of normal activity in vitro (example, Koleske_2022). The following publication has been ascertained in the context of this evaluation (PMID: 36343260). ClinVar contains an entry for this variant (Variation ID: 460410). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Natera, |
RCV000554108 | SCV001458332 | uncertain significance | Renal carnitine transport defect | 2020-05-01 | no assertion criteria provided | clinical testing |