Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002035333 | SCV002232275 | pathogenic | Renal carnitine transport defect | 2024-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 280 of the SLC22A5 protein (p.Ser280Phe). This variant is present in population databases (rs386134208, gnomAD 0.006%). This missense change has been observed in individual(s) with primary carnitine deficiency (PMID: 28841266, 29132460). ClinVar contains an entry for this variant (Variation ID: 1451545). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SLC22A5 function (PMID: 28841266). This variant disrupts the p.Ser280 amino acid residue in SLC22A5. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV002035333 | SCV004201256 | likely pathogenic | Renal carnitine transport defect | 2024-03-19 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002035333 | SCV005669217 | pathogenic | Renal carnitine transport defect | 2024-05-10 | criteria provided, single submitter | clinical testing |