Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics Munich, |
RCV000578309 | SCV000680375 | pathogenic | Biotin-responsive basal ganglia disease | 2017-12-11 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000578309 | SCV004294034 | pathogenic | Biotin-responsive basal ganglia disease | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 181 of the SLC19A3 protein (p.Ser181Pro). This variant is present in population databases (rs773971505, gnomAD 0.07%). This missense change has been observed in individual(s) with clinical features of biotin-responsive basal ganglia disease (PMID: 23482991, 26863430, 28856750). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 488596). 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 SLC19A3 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |