ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.197T>G (p.Met66Arg)

gnomAD frequency: 0.00001  dbSNP: rs587783002
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000144056 SCV002263079 pathogenic Biotinidase deficiency 2023-08-04 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 86 of the BTD protein (p.Met86Arg). This variant is present in population databases (rs587783002, gnomAD 0.0009%). This missense change has been observed in individual(s) with partial biotinidase deficiency (PMID: 24797656, 25144890, 26361991). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 156000). 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. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003323415 SCV004029301 uncertain significance not specified 2023-07-18 criteria provided, single submitter clinical testing Variant summary: BTD c.197T>G (p.Met66Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251402 control chromosomes (gnomAD). c.197T>G has been reported in the literature in individuals affected with Partial Biotinidase Deficiency (examples: Li_2014, Jay_2015 and Gannavarapu_2015). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26361991, 25144890, 24797656). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Baylor Genetics RCV000144056 SCV004211450 likely pathogenic Biotinidase deficiency 2023-07-03 criteria provided, single submitter clinical testing
Molecular Genetics Diagnostic Laboratory, Detroit Medical Center University Laboratories RCV000144056 SCV000189129 pathogenic Biotinidase deficiency no assertion criteria provided clinical testing

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