Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000022015 | SCV000800642 | uncertain significance | Biotinidase deficiency | 2017-12-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000022015 | SCV000832890 | pathogenic | Biotinidase deficiency | 2023-11-22 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 485 of the BTD protein (p.His485Gln). This variant is present in population databases (rs201604102, gnomAD 0.02%). This missense change has been observed in individual(s) with profound biotinidase deficiency (PMID: 25967232, 26810761, 30912303; 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: 25090). 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 not expected to disrupt BTD protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Mendelics | RCV000022015 | SCV001136349 | pathogenic | Biotinidase deficiency | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV002477005 | SCV002774329 | pathogenic | not provided | 2021-08-13 | criteria provided, single submitter | clinical testing | The variant has been reported in individuals with reduced biotinidase activity in the published literature, including in a homozygous child with profound biotinidase deficiency (PMID: 25967232 (2015), 26810761 (2016), 30912303 (2019), 31801038 (2020)). Therefore, the variant is classified as pathogenic. |
| Ambry Genetics | RCV002513165 | SCV003589835 | likely pathogenic | Inborn genetic diseases | 2022-01-31 | criteria provided, single submitter | clinical testing | The c.1455C>G (p.H485Q) alteration is located in exon 4 (coding exon 4) of the BTD gene. This alteration results from a C to G substitution at nucleotide position 1455, causing the histidine (H) at amino acid position 485 to be replaced by a glutamine (Q). Based on data from gnomAD, the G allele has an overall frequency of <0.01% (5/282840) total alleles studied. The highest observed frequency was 0.02% (5/24966) of African alleles. This alteration has been detected as homozygous and as compound heterozygous with another BTD pathogenic mutation in individuals with profound biotinidase deficiency (Lara, 2015; Procter, 2016). This amino acid position is not well conserved in available vertebrate species, and glutamine is the reference amino acid in some other vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |
| Baylor Genetics | RCV000022015 | SCV004211452 | likely pathogenic | Biotinidase deficiency | 2023-06-22 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000022015 | SCV001461227 | likely pathogenic | Biotinidase deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |