ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.1415C>T (p.Thr472Ile)

dbSNP: rs796051941
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV003414156 SCV004109301 uncertain significance BTD-related disorder 2023-04-13 criteria provided, single submitter clinical testing The BTD c.1475C>T variant is predicted to result in the amino acid substitution p.Thr492Ile. This variant was reported along with the common c.1330G>C (p.Asp444His) partial deficiency variant in a patient with partial biotinidase deficiency. His biotinidase enzyme activity level was reportedly ~16% of control, suggesting the c.1475C>T (p.Thr492Ile) substitution may be a severe variant (Tonin et al. 2015. PubMed ID: 25795614). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating it is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp RCV003497997 SCV004293428 likely pathogenic Biotinidase deficiency 2023-08-07 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 492 of the BTD protein (p.Thr492Ile). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 25795614). This variant is not present in population databases (gnomAD no frequency).

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