Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Giacomini Lab, |
RCV002286657 | SCV002576666 | uncertain significance | Renal carnitine transport defect | 2022-10-03 | criteria provided, single submitter | research | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002286657 | SCV004039070 | likely pathogenic | Renal carnitine transport defect | 2023-08-11 | criteria provided, single submitter | clinical testing | Variant summary: SLC22A5 c.700G>C (p.Gly234Arg) 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 4e-06 in 251488 control chromosomes (gnomAD). c.700G>C has been reported in the literature as a biallelic genotype in individuals affected with Systemic Primary Carnitine Deficiency (e.g. Lee_2010, Han_2014). These data indicate that the variant may be associated with disease. When carnitine uptake activity was assayed using transiently transfected HEK293T cells, the variant was shown to significantly reduce transport activity (0.25%) compared to wild-type (Koleske_2022). The following publications have been ascertained in the context of this evaluation (PMID: 25132046, 36343260, 20074989). One ClinVar submitter has assessed the variant since 2014, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Baylor Genetics | RCV002286657 | SCV004203584 | pathogenic | Renal carnitine transport defect | 2023-02-03 | criteria provided, single submitter | clinical testing |