ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.641C>T (p.Thr214Ile) (rs587783005)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000144060 SCV000915027 likely pathogenic Biotinidase deficiency 2017-10-09 criteria provided, single submitter clinical testing The BTD c.701C>T (p.Thr234Ile) missense variant has been reported in at least three individuals, including in a homozygous state in one individual with profound biotinidase deficiency, and in a compound heterozygous state in two individuals, including one with profound and one with partial biotinidase deficiency (Li et al. 2014; Wolf et al. 2017). Control data are unavailable for this variant, which is reported at a frequency of 0.00026 in the South Asian population of the Genome Aggregation Database. Based on the evidence, the p.Thr234Ile variant is classified as likely pathogenic for biotinidase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000144060 SCV000933006 pathogenic Biotinidase deficiency 2018-10-24 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 234 of the BTD protein (p.Thr234Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs587783005, ExAC 0.02%). This variant has been observed to be homozygous or in combination with another BTD variant in individuals affected with biotinidase deficiency (PMID: 24797656, 27657684) and in one of those individuals it has been observed on the opposite chromosome (in trans) from another pathogenic variant. 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: 156003). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Diagnostic Laboratory,Detroit Medical Center University Laboratories RCV000144060 SCV000189133 pathogenic Biotinidase deficiency no assertion criteria provided clinical testing
Research and Development, ARUP Laboratories RCV000144060 SCV000845814 pathogenic Biotinidase deficiency 2017-02-17 no assertion criteria provided literature only Enzyme activities @ 2.3 U/L with c.1330G>C;p.D444H in one patient. Enzyme activity @ 0.8 U/L in a homozygous patient.

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.