ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.566G>A (p.Arg189His)

gnomAD frequency: 0.00007  dbSNP: rs398123139
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) 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, Molecular Genetics and Genomics, 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.
Invitae 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, University Hospital Tübingen 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 2023-08-30 criteria provided, single submitter clinical testing
Molecular Genetics Diagnostic Laboratory, Detroit Medical Center University Laboratories RCV000144058 SCV000189131 pathogenic Biotinidase deficiency no assertion criteria provided clinical testing
Natera, Inc. RCV000144058 SCV001461218 pathogenic Biotinidase deficiency 2020-09-16 no assertion criteria provided clinical testing

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