ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.176G>A (p.Arg59His)

gnomAD frequency: 0.00001  dbSNP: rs397514343
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000021905 SCV000800614 uncertain significance Biotinidase deficiency 2017-11-14 criteria provided, single submitter clinical testing
Invitae RCV000021905 SCV001411319 pathogenic Biotinidase deficiency 2023-09-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 79 of the BTD protein (p.Arg79His). This variant is present in population databases (rs397514343, gnomAD 0.003%). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 14707518). 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: 38567). 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 variant disrupts the p.Arg79 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10801053, 15060693, 27845546, 29359854). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Suma Genomics RCV000021905 SCV002543789 pathogenic Biotinidase deficiency criteria provided, single submitter clinical testing
GeneDx RCV003125847 SCV003803151 likely pathogenic not provided 2022-07-14 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.236 G>A (79 R>H); This variant is associated with the following publications: (PMID: 14707518, 15060693)
Baylor Genetics RCV000021905 SCV004211432 likely pathogenic Biotinidase deficiency 2023-08-22 criteria provided, single submitter clinical testing
Natera, Inc. RCV000021905 SCV002081545 likely pathogenic Biotinidase deficiency 2020-09-09 no assertion criteria provided clinical testing

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