Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001975156 | SCV002244778 | pathogenic | Renal carnitine transport defect | 2021-01-02 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this variant affects SLC22A5 protein function (PMID: 11058897). For these reasons, this variant has been classified as Pathogenic. 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. This variant has been observed in individual(s) with primary carnitine deficiency (PMID: 11058897). ClinVar contains an entry for this variant (Variation ID: 25405). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with aspartic acid at codon 301 of the SLC22A5 protein (p.Ala301Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001975156 | SCV002600507 | pathogenic | Renal carnitine transport defect | 2022-10-14 | criteria provided, single submitter | clinical testing | Variant summary: SLC22A5 c.902C>A (p.Ala301Asp) 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 was absent in 251496 control chromosomes (gnomAD). c.902C>A has been reported in the literature in at least one homozygous individual affected with Systemic Primary Carnitine Deficiency (e.g. Wang_2000, Frigeni_2017). Experimental evidence demonstrated the variant affects protein function, leading to residual carnitine transport activity that was <10% of wild-type. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |