Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000021994 | SCV000800681 | uncertain significance | Biotinidase deficiency | 2018-03-27 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000021994 | SCV000938428 | pathogenic | Biotinidase deficiency | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 418 of the BTD protein (p.Cys418Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 26810761, 27329734; 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: 25069). 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.Cys418 amino acid residue in BTD. Other variant(s) that disrupt this residue have been observed in individuals with BTD-related conditions (PMID: 14707518), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000021994 | SCV004211445 | likely pathogenic | Biotinidase deficiency | 2024-01-25 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000021994 | SCV005660293 | pathogenic | Biotinidase deficiency | 2024-04-12 | criteria provided, single submitter | clinical testing |