ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.410G>A (p.Arg137His)

gnomAD frequency: 0.00016  dbSNP: rs146015592
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000078072 SCV000230012 pathogenic not provided 2016-10-26 criteria provided, single submitter clinical testing
GeneDx RCV000078072 SCV000329674 pathogenic not provided 2021-01-08 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 11668630, 25423671, 26361991, 27657684, 33123633, 32440248, 33189081, 9396567, 23644139, 25754625, 34426522)
Invitae RCV000021904 SCV000754949 pathogenic Biotinidase deficiency 2024-01-18 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 157 of the BTD protein (p.Arg157His). This variant is present in population databases (rs146015592, gnomAD 0.02%). This missense change has been observed in individual(s) with biotinidase deficicency (PMID: 9396567, 11313766, 20224900, 22698809). 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: 38290). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000078072 SCV000888018 pathogenic not provided 2022-09-16 criteria provided, single submitter clinical testing In the published literature, this variant has reported as one of the most common pathogenic variants associated with biotinidase deficiency in Turkish population (PMIDs: 25754625 (2015), 29353266 (2018), and 33189081 (2021)). This variant has been identified in homozygous state or compound heterozygous state with other pathogenic BTD variants in multiple individuals with profound to partial biotinidase deficiency (PMIDs: 9396567 (1997), 10801053 (2000), 11313766 (2001), 16435182 (2005), 22698809 (2012), 25754625 (2015), 27329734, (2016), 29353266 (2018), and 33189081 (2021)). Therefore, this individual is at least a carrier of biotinidase deficiency.
Myriad Genetics, Inc. RCV000021904 SCV001193882 pathogenic Biotinidase deficiency 2019-12-24 criteria provided, single submitter clinical testing NM_000060.2(BTD):c.470G>A(R157H) is classified as pathogenic in the context of biotinidase deficiency. Please note that R157H is seen in patients with both partial and profound biotinidase deficiency. Sources cited for classification include the following: PMID 23644139, 11313766, 16435182, 25754625, 9396567, 27329734 and 26361991. Classification of NM_000060.2(BTD):c.470G>A(R157H) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
DASA RCV000021904 SCV002061179 pathogenic Biotinidase deficiency 2022-01-05 criteria provided, single submitter clinical testing The c.410G>A;p.(Arg137His) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (Clinvar ID: 38290; PMID: 27329734; 26361991; 25754625; 23644139; 22698809; 20224900; 11313766) - PS4.The variant is located in a mutational hot spot and/or critical and well-established functional domain (CN_hydrolase domain) - PM1. The variant is present at low allele frequencies population databases (rs146015592– gnomAD 0.001514%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Arg137His) was detected in trans with a pathogenic variant (PMID: 27329734; 26361991; 25754625; 23644139; 22698809; 20224900; 11313766) - PM3_strong. Pathogenic missense variant in this residue have been reported (Clinvar ID: 25012) - PM5. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic.
Baylor Genetics RCV000021904 SCV004211386 pathogenic Biotinidase deficiency 2023-10-31 criteria provided, single submitter clinical testing
Natera, Inc. RCV000021904 SCV001460182 pathogenic Biotinidase deficiency 2020-09-16 no assertion criteria provided clinical testing

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