ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.364C>A (p.Pro122Thr)

dbSNP: rs397514357
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000438885 SCV000521148 likely pathogenic not provided 2016-11-10 criteria provided, single submitter clinical testing The P142T pathogenic variant in the BTD gene has been reported previously in the compound heterozygous and homozygous states in individuals with biotinidase deficiency (Sarafoglou et al., 2009; Gannavarapu et al., 2015). The P142T variant is not observed in large population cohorts (Lek et al., 2016; Exome Variant Server). The P142T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The P142T variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000021923 SCV000996436 likely pathogenic Biotinidase deficiency 2019-07-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV001266904 SCV001445084 uncertain significance Inborn genetic diseases 2019-03-20 criteria provided, single submitter clinical testing The alteration results in an amino acid change:_x000D_ _x000D_ The c.424C>A (p.P142T) alteration is located in coding exon 3 of the BTD gene. This alteration results from a C to A substitution at nucleotide position 424, causing the proline (P) at amino acid position 142 to be replaced by a threonine (T). The alteration is not observed in population databases:_x000D_ _x000D_ Based on data from the Genome Aggregation Database (gnomAD), the BTD c.424C>A alteration was not observed with coverage at this location. The amino acid change has been observed in affected individuals: _x000D_ _x000D_ The p.P142T alteration has been reported heterozygous with a second alteration in the BTD gene and homozygous in patients with profound biotinidase deficiency. The majority of reported patients with this alteration to date are of Somali heritage (Sarafoglou, 2009; Gannavarapu, 2015). The altered amino acid is conserved throughout evolution:_x000D_ _x000D_ The p.P142 amino acid is conserved in available vertebrate species. The alteration is predicted deleterious by in silico models:_x000D_ _x000D_ The p.P142T alteration is predicted to be probably damaging by Polyphen and deleterious by SIFT in silico analyses. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Invitae RCV000021923 SCV002228733 pathogenic Biotinidase deficiency 2023-08-30 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 19757147, 26361991, 26589311). ClinVar contains an entry for this variant (Variation ID: 25004). 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 142 of the BTD protein (p.Pro142Thr).
PreventionGenetics, part of Exact Sciences RCV003904859 SCV004726478 pathogenic BTD-related disorder 2023-11-02 criteria provided, single submitter clinical testing The BTD c.424C>A variant is predicted to result in the amino acid substitution p.Pro142Thr. This variant is absent from a large population database (, indicating it is rare. Furthermore, it has been reported in the homozygous or compound heterozygous state in several patients with profound biotinidase deficiency (Sarafoglou et al. 2009. PubMed ID: 19757147; Al-Jasmi et al. 2016. PubMed ID: 26589311; Gannavarapu et al. 2015. PubMed ID: 26361991; Tangeraas et al. 2020. PubMedID: 33123633). Taken together, we interpret this variant as pathogenic.
Counsyl RCV000021923 SCV000796708 likely pathogenic Biotinidase deficiency 2017-12-28 no assertion criteria provided clinical testing

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