Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000507456 | SCV000109914 | pathogenic | not provided | 2018-08-21 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000507456 | SCV000600944 | pathogenic | not provided | 2020-07-09 | criteria provided, single submitter | clinical testing | The variant has been found in at least one symptomatic patient. The variant occurs in multiple cases with a lone recessive pathogenic/likely pathogenic variant in the same gene, and several have phenotype known to be consistent with disease. |
ARUP Laboratories, |
RCV000144058 | SCV000602898 | pathogenic | Biotinidase deficiency | 2023-10-02 | criteria provided, single submitter | clinical testing | The BTD c.566G>A; p.Arg189His variant (rs398123139), also known as c.626G>A; p.Arg209His for NM_000060.2, has been reported in an individual with profound BTD deficiency, and found in-trans with a pathogenic variant (Li 2014). Another missense variant at this residue, p.Arg189Cys, has been reported in an individual with partial BTD deficiency when found with a pathogenic variant (Procter 2016). The p.Arg189His variant is reported in ClinVar (Variation ID: 92400). It is observed in the general population with an overall allele frequency of 0.002% (7/282856 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is deleterious (REVEL: 0.84). Based on the available information, the p.Arg189His variant is considered to be pathogenic. References: Li H et al. Novel mutations causing biotinidase deficiency in individuals identified by newborn screening in Michigan including an unique intronic mutation that alters mRNA expression of the biotinidase gene. Mol Genet Metab. 2014 Jul;112(3):242-6. PMID: 24797656. Procter M et al. Forty-eight novel mutations causing biotinidase deficiency. Mol Genet Metab. 2016 Mar;117(3):369-72. PMID: 26810761. |
Labcorp Genetics |
RCV000144058 | SCV000940981 | pathogenic | Biotinidase deficiency | 2023-09-24 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 92400). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg209 amino acid residue in BTD. Other variant(s) that disrupt this residue have been observed in individuals with BTD-related conditions (PMID: 24797656, 25754625, 26361991, 26810761), which suggests that this may be a clinically significant amino acid residue. 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 missense change has been observed in individual(s) with biotinidase deficiency (PMID: 24797656, 25754625, 26361991). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs398123139, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 209 of the BTD protein (p.Arg209His). |
Institute of Medical Genetics and Applied Genomics, |
RCV000507456 | SCV001446641 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
MGZ Medical Genetics Center | RCV000144058 | SCV002580763 | pathogenic | Biotinidase deficiency | 2022-03-04 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000144058 | SCV004211431 | pathogenic | Biotinidase deficiency | 2024-03-24 | criteria provided, single submitter | clinical testing | |
Molecular Genetics Diagnostic Laboratory, |
RCV000144058 | SCV000189131 | pathogenic | Biotinidase deficiency | no assertion criteria provided | clinical testing | ||
Natera, |
RCV000144058 | SCV001461218 | pathogenic | Biotinidase deficiency | 2020-09-16 | no assertion criteria provided | clinical testing | |
Prevention |
RCV003905037 | SCV004725007 | pathogenic | BTD-related disorder | 2023-10-28 | no assertion criteria provided | clinical testing | The BTD c.626G>A variant is predicted to result in the amino acid substitution p.Arg209His. This variant has been reported in the compound heterozygous state in individuals with biotinidase deficiency (Gannavarapu et al. 2015. PubMed ID: 26361991; Li et al. 2014. PubMed ID: 24797656; Karaca et al. 2015. PubMed ID: 25754625; Al-Jasmi et al. 2015. PubMed ID: 26589311). In vitro experimental studies suggest this variant impacts protein function (Li et al. 2014. PubMed ID: 24797656). An alternate nucleotide change affecting the same amino acid (p.Arg209Cys) has been reported in individuals with biotinidase deficiency (Procter et al. 2016. PubMed ID: 26810761; Kars et al. 2021. PubMed ID: 34426522). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-15685989-G-A). This variant is interpreted as pathogenic. |