Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000811626 | SCV000951901 | uncertain significance | Renal carnitine transport defect | 2024-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 455 of the SLC22A5 protein (p.Pro455Arg). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with abnormal newborn screening results (PMID: 20574985, 28841266). ClinVar contains an entry for this variant (Variation ID: 655449). 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%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV001570976 | SCV001795355 | likely pathogenic | not provided | 2020-12-11 | criteria provided, single submitter | clinical testing | Reported previously in an individual with an abnormal newborn screening result; a second variant in the SLC22A5 gene was not identified (Li et al., 2010); Published functional studies in CHO cells revealed that P455R exhibited 18% activity compared to wild-type (Frigeni et al., 2017); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20574985, 28841266) |
| Genome- |
RCV000811626 | SCV002055774 | likely pathogenic | Renal carnitine transport defect | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000811626 | SCV004029482 | likely pathogenic | Renal carnitine transport defect | 2023-07-28 | criteria provided, single submitter | clinical testing | Variant summary: SLC22A5 c.1364C>G (p.Pro455Arg) 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 251470 control chromosomes (gnomAD). c.1364C>G has been reported in the literature in an infant with abnormal NBS result (example: Li_2010). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (example: Frigeni_2017). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=1) and likely pathogenic (n=2). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV000811626 | SCV004201279 | likely pathogenic | Renal carnitine transport defect | 2024-02-20 | criteria provided, single submitter | clinical testing |