Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000022007 | SCV000630325 | pathogenic | Biotinidase deficiency | 2023-09-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 445 of the BTD protein (p.Gly445Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with both profound and partial biotinidase deficiency (PMID: 9396567, 15776412). 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: 25082). 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 BTD protein function. This variant disrupts the p.Gly445 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20224900). 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985644 | SCV001134038 | pathogenic | not provided | 2019-05-03 | criteria provided, single submitter | clinical testing | Not found in the total gnomAD dataset, and the data is high quality (0/282830 chr). Found in at least two symptomatic patients. Predicted to have a damaging effect on the protein. Occurs in multiple cases with a recessive pathogenic variant in the same gene. Assessment of experimental evidence suggests this variant results in abnormal protein function. |
| Baylor Genetics | RCV000022007 | SCV004211428 | likely pathogenic | Biotinidase deficiency | 2023-09-08 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000022007 | SCV002081576 | pathogenic | Biotinidase deficiency | 2021-04-19 | no assertion criteria provided | clinical testing |