Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000021962 | SCV000800684 | uncertain significance | Biotinidase deficiency | 2018-03-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000021962 | SCV002266868 | likely pathogenic | Biotinidase deficiency | 2023-08-21 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 255 of the BTD protein (p.Ile255Thr). This variant is present in population databases (rs397514384, gnomAD 0.002%). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 20224900, 25144890; Invitae). 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: 25040). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000021962 | SCV003922836 | likely pathogenic | Biotinidase deficiency | 2023-03-17 | criteria provided, single submitter | clinical testing | Variant summary: BTD c.704T>C (p.Ile235Thr) results in a non-conservative amino acid change located in the Carbon-nitrogen hydrolase domain (IPR003010) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251440 control chromosomes (gnomAD). c.704T>C has been reported in the literature in at least three compound heterozygous individuals affected with Biotinidase Deficiency (Ohlsson_2010, Jay_2015), who carried a pathogenic variant in trans. In one of the reported patients the biotinidase activity in plasma was immeasurable, suggesting this variant results in profound Biotinidase deficiency (Ohlsson_2010). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as likely pathogenic, or as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV000021962 | SCV004211490 | likely pathogenic | Biotinidase deficiency | 2022-05-09 | criteria provided, single submitter | clinical testing |