ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.281G>T (p.Gly94Val)

gnomAD frequency: 0.00001  dbSNP: rs375712490
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000021918 SCV000796685 likely pathogenic Biotinidase deficiency 2017-12-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759007 SCV000888016 pathogenic not provided 2015-12-22 criteria provided, single submitter clinical testing
Mendelics RCV000021918 SCV001136340 pathogenic Biotinidase deficiency 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000021918 SCV001228394 pathogenic Biotinidase deficiency 2025-01-29 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 114 of the BTD protein (p.Gly114Val). This variant is present in population databases (rs375712490, gnomAD 0.006%). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 15776412, 20083419, 27657684). ClinVar contains an entry for this variant (Variation ID: 24999). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt BTD protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000021918 SCV002548198 pathogenic Biotinidase deficiency 2022-05-12 criteria provided, single submitter clinical testing Variant summary: BTD c.281G>T (p.Gly94Val) 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 1.2e-05 in 250516 control chromosomes. c.281G>T has been reported in the literature in individuals affected with Biotinidase Deficiency (Iqbal_2010, Wolf_2017, Carvalho_2020, Maguolo_2021, Milankovics_2010). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Ambry Genetics RCV002513162 SCV003697228 pathogenic Inborn genetic diseases 2022-03-23 criteria provided, single submitter clinical testing The c.341G>T (p.G114V) alteration is located in exon 3 (coding exon 3) of the BTD gene. This alteration results from a G to T substitution at nucleotide position 341, causing the glycine (G) at amino acid position 114 to be replaced by a valine (V). Based on data from gnomAD, the T allele has an overall frequency of <0.01% (3/250516) total alleles studied. The highest observed frequency was 0.01% (2/34484) of Latino alleles. This alteration has been reported in the homozygous and compound heterozygous states in individuals with biotinidase deficiency (Iqbal, 2010; Maguolo, 2021; Wolf, 2005). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.
GeneDx RCV000759007 SCV004167846 pathogenic not provided 2023-04-06 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as c.341G>T, p.(G114V); This variant is associated with the following publications: (PMID: 15776412, 25087612, 31801038, 34136440, 36684547, 29353266, 20549359, 20083419, 27657684)
Baylor Genetics RCV000021918 SCV004211419 pathogenic Biotinidase deficiency 2023-10-03 criteria provided, single submitter clinical testing
Natera, Inc. RCV000021918 SCV001460180 pathogenic Biotinidase deficiency 2020-09-16 no assertion criteria provided clinical testing

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