ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.572G>A (p.Arg191His)

gnomAD frequency: 0.00001  dbSNP: rs112195009
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000078077 SCV000109915 uncertain significance not provided 2017-07-21 criteria provided, single submitter clinical testing
Counsyl RCV000021951 SCV000800581 uncertain significance Biotinidase deficiency 2017-08-21 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000078077 SCV001246040 likely pathogenic not provided 2024-10-01 criteria provided, single submitter clinical testing BTD: PM3:Strong, PM1, PM2, PM5, BP4
Labcorp Genetics (formerly Invitae), Labcorp RCV000021951 SCV001400277 pathogenic Biotinidase deficiency 2023-12-30 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 211 of the BTD protein (p.Arg211His). This variant is present in population databases (rs112195009, gnomAD 0.02%). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 26361991; Invitae). ClinVar contains an entry for this variant (Variation ID: 25029). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BTD protein function. This variant disrupts the p.Arg211 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10400129, 17185019, 25754625, 26810761, 27329734). 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.
Baylor Genetics RCV000021951 SCV004211404 likely pathogenic Biotinidase deficiency 2024-03-19 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004751220 SCV005346220 likely pathogenic BTD-related disorder 2024-07-10 no assertion criteria provided clinical testing The BTD c.632G>A variant is predicted to result in the amino acid substitution p.Arg211His. This variant, also described as c.572G>A (p.Arg191His), has been reported in the heterozygous and compound heterozygous states in multiple individuals with biotinidase deficiency (Thodi et al. 2011. PubMed ID: 22011816; Gannavarapu et al. 2015. PubMed ID: 26361991; Porta et al. 2017. PubMed ID: 28971021). This variant is reported in 0.015% of alleles in individuals of East Asian descent in gnomAD. Alternate missense changes affecting the same amino acid (p.Arg211Cys, p.Arg211Ser, and p.Arg211Leu) have been reported in multiple individuals with biotinidase deficiency (Norrgard et al. 1999. PubMed ID: 10400129; Carvalho et al. 2019. PubMed ID: 30912303). This variant is interpreted as likely pathogenic.

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