ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.425C>T (p.Ala142Val)

gnomAD frequency: 0.00001  dbSNP: rs397514364
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000021934 SCV002049838 pathogenic Biotinidase deficiency 2021-11-09 criteria provided, single submitter clinical testing The BTD c.485C>T; p.Ala162Val variant (rs397514364) is reported in the literature in multiple individuals affected with partial to profound biotinidase deficiency usually found with a second pathogenic variant (Norrgard 1999, Wolf 2017). This variant is reported in ClinVar (Variation ID: 25014) and is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The alanine at codon 162 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.928). Based on available information, this variant is considered to be pathogenic. References: Norrgard KJ et al. Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children. Pediatr Res. 1999 Jul;46(1):20-7. PMID: 10400129. Wolf B et al. Successful outcomes of older adolescents and adults with profound biotinidase deficiency identified by newborn screening. Genet Med. 2017 Apr;19(4):396-402. PMID: 27657684.
Labcorp Genetics (formerly Invitae), Labcorp RCV000021934 SCV002313747 pathogenic Biotinidase deficiency 2023-10-11 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 162 of the BTD protein (p.Ala162Val). This variant is present in population databases (rs397514364, gnomAD 0.0009%). This missense change has been observed in individual(s) with BTD-related conditions (PMID: 25144890, 27657684). ClinVar contains an entry for this variant (Variation ID: 25014). 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.
Baylor Genetics RCV000021934 SCV004211478 pathogenic Biotinidase deficiency 2023-11-22 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000021934 SCV005660270 likely pathogenic Biotinidase deficiency 2024-02-02 criteria provided, single submitter clinical testing
Counsyl RCV000021934 SCV000800682 uncertain significance Biotinidase deficiency 2018-03-26 flagged submission clinical testing

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