Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000704791 | SCV000833755 | uncertain significance | Renal carnitine transport defect | 2022-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 149 of the SLC22A5 protein (p.Phe149Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SLC22A5-related conditions (PMID: 28711408, 32778825; Invitae). ClinVar contains an entry for this variant (Variation ID: 581072). 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 not expected to disrupt SLC22A5 protein function. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004702356 | SCV005203133 | uncertain significance | not specified | 2024-07-09 | criteria provided, single submitter | clinical testing | Variant summary: SLC22A5 c.447C>G (p.Phe149Leu) results in a non-conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251496 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.447C>G has been reported in the literature in at-least one individual affected with Systemic Primary Carnitine Deficiency (example: Gallant_2017). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 28711408). ClinVar contains an entry for this variant (Variation ID: 581072). Based on the evidence outlined above, the variant was classified as uncertain significance. |