ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.566G>A (p.Arg189His) (rs398123139)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics 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 best available variant frequency is uninformative because it is below the disease allele frequency. Found in at least one patient with expected phenotype for this gene. Conflicting predictions of the effect on the protein. Located in potentially critical domain of the protein. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. This variant is statistically more frequent in affected individuals than in the general population and/or healthy controls. One other pathogenic or likely pathogenic variant affects the same amino acid.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000185803 SCV000602898 pathogenic not specified 2017-02-16 criteria provided, single submitter clinical testing
Invitae RCV000144058 SCV000940981 pathogenic Biotinidase deficiency 2018-08-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 209 of the BTD protein (p.Arg209His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs398123139, ExAC 0.02%). This variant has been observed on the opposite chromosome (in trans) or in combination (phase unknown) from other pathogenic variants in several individuals affected with biotinidase deficiency (PMID: 24797656, 25754625, 26361991). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 92400). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The observation of one or more missense substitutions at this codon (p.Arg209Cys and p.Arg209His) in affected individuals suggests that this may be a clinically significant residue (PMID: 26810761, 24797656, 25754625, 26361991). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000507456 SCV001446641 pathogenic not provided 2020-10-23 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
Research and Development, ARUP Laboratories RCV000144058 SCV000845808 pathogenic Biotinidase deficiency 2017-02-17 no assertion criteria provided literature only Enzyme activity @ 0.8 U/L. Seen with c.1368A>C;p.Q456H.
Natera, Inc. RCV000144058 SCV001461218 pathogenic Biotinidase deficiency 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.