Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002035333 | SCV002232275 | pathogenic | Renal carnitine transport defect | 2020-11-05 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with phenylalanine at codon 280 of the SLC22A5 protein (p.Ser280Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs386134208, ExAC 0.001%). Experimental studies have shown that this variant affects SLC22A5 protein function (PMID: 28841266). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser280 amino acid residue in SLC22A5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 28841266, 29132460). ClinVar contains an entry for this variant (Variation ID: 25398). |
| Baylor Genetics | RCV002035333 | SCV004201256 | likely pathogenic | Renal carnitine transport defect | 2023-10-22 | criteria provided, single submitter | clinical testing |