ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.1553G>A (p.Arg518His)

gnomAD frequency: 0.00001  dbSNP: rs397514429
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000022024 SCV001588464 pathogenic Biotinidase deficiency 2023-07-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg538 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9099842, 22698809, 27207447, 27657684). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects BTD function (PMID: 29359854). 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. ClinVar contains an entry for this variant (Variation ID: 25099). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 19757147, 26810761, 29359854; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs397514429, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 538 of the BTD protein (p.Arg538His).
Revvity Omics, Revvity Omics RCV000022024 SCV002022093 likely pathogenic Biotinidase deficiency 2023-01-17 criteria provided, single submitter clinical testing
Baylor Genetics RCV000022024 SCV004211480 likely pathogenic Biotinidase deficiency 2023-01-30 criteria provided, single submitter clinical testing

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