Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000078077 | SCV000109915 | uncertain significance | not provided | 2017-07-21 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000021951 | SCV000800581 | uncertain significance | Biotinidase deficiency | 2017-08-21 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000078077 | SCV001246040 | likely pathogenic | not provided | 2024-10-01 | criteria provided, single submitter | clinical testing | BTD: PM3:Strong, PM1, PM2, PM5, BP4 |
Labcorp Genetics |
RCV000021951 | SCV001400277 | pathogenic | Biotinidase deficiency | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 211 of the BTD protein (p.Arg211His). This variant is present in population databases (rs112195009, gnomAD 0.02%). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 26361991; Invitae). ClinVar contains an entry for this variant (Variation ID: 25029). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BTD protein function. This variant disrupts the p.Arg211 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10400129, 17185019, 25754625, 26810761, 27329734). 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. |
Baylor Genetics | RCV000021951 | SCV004211404 | likely pathogenic | Biotinidase deficiency | 2024-03-19 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004751220 | SCV005346220 | likely pathogenic | BTD-related disorder | 2024-07-10 | no assertion criteria provided | clinical testing | The BTD c.632G>A variant is predicted to result in the amino acid substitution p.Arg211His. This variant, also described as c.572G>A (p.Arg191His), has been reported in the heterozygous and compound heterozygous states in multiple individuals with biotinidase deficiency (Thodi et al. 2011. PubMed ID: 22011816; Gannavarapu et al. 2015. PubMed ID: 26361991; Porta et al. 2017. PubMed ID: 28971021). This variant is reported in 0.015% of alleles in individuals of East Asian descent in gnomAD. Alternate missense changes affecting the same amino acid (p.Arg211Cys, p.Arg211Ser, and p.Arg211Leu) have been reported in multiple individuals with biotinidase deficiency (Norrgard et al. 1999. PubMed ID: 10400129; Carvalho et al. 2019. PubMed ID: 30912303). This variant is interpreted as likely pathogenic. |