Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000186157 | SCV000239183 | pathogenic | not provided | 2020-08-14 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect based on significantly reduced carnitine transport (Rose et al., 2012); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 21922592, 20027113, 20574985, 28841266) |
Labcorp Genetics |
RCV000006797 | SCV000632521 | pathogenic | Renal carnitine transport defect | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 442 of the SLC22A5 protein (p.Ala442Ile). This variant is present in population databases (rs267607053, gnomAD 0.001%). This missense change has been observed in individual(s) with primary carnitine deficiency and systemic carnitine deficiency (PMID: 20027113, 21922592, 28841266). ClinVar contains an entry for this variant (Variation ID: 6428). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000006797 | SCV002055827 | pathogenic | Renal carnitine transport defect | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000006797 | SCV002809341 | likely pathogenic | Renal carnitine transport defect | 2022-03-18 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000006797 | SCV003821053 | pathogenic | Renal carnitine transport defect | 2022-01-27 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000006797 | SCV004201304 | pathogenic | Renal carnitine transport defect | 2024-02-19 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000006797 | SCV005203886 | pathogenic | Renal carnitine transport defect | 2024-07-30 | criteria provided, single submitter | clinical testing | Variant summary: SLC22A5 c.1324_1325delinsAT (p.Ala442Ile) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.8e-05 in 1614054 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in SLC22A5 causing Systemic Primary Carnitine Deficiency (3.8e-05 vs 0.0046), allowing no conclusion about variant significance. c.1324_1325delinsAT has been reported in the literature in the homozygous and compound heterozygous states in individuals affected with Systemic Primary Carnitine Deficiency (e.g. Frigeni_2017, El-Hattab_2010, Ambroze_2022). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence that this variant causes reduced carnitine transport activity in vitro and in vivo (e.g. Frigeni_2017). The following publications have been ascertained in the context of this evaluation (PMID: 36109795, 20027113, 28841266). ClinVar contains an entry for this variant (Variation ID: 6428). Based on the evidence outlined above, the variant was classified as pathogenic. |
OMIM | RCV000006797 | SCV000026993 | pathogenic | Renal carnitine transport defect | 2015-04-29 | no assertion criteria provided | literature only | |
Counsyl | RCV000006797 | SCV001132489 | uncertain significance | Renal carnitine transport defect | 2019-01-24 | no assertion criteria provided | clinical testing |