ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.410G>A (p.Arg137His)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001370658.1(BTD):c.410G>A (p.Arg137His)
Variation ID: 38290 Accession: VCV000038290.24
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 3p25.1 3: 15644326 (GRCh38) [ NCBI UCSC ] 3: 15685833 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 6, 2016 Jun 17, 2024 Mar 25, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001370658.1:c.410G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.Arg137His missense NM_000060.4:c.470G>A NP_000051.1:p.Arg157His missense NM_001281723.4:c.410G>A NP_001268652.2:p.Arg137His missense NM_001281724.3:c.410G>A NP_001268653.2:p.Arg137His missense NM_001281725.3:c.410G>A NP_001268654.1:p.Arg137His missense NM_001323582.2:c.410G>A NP_001310511.1:p.Arg137His missense NM_001370752.1:c.410G>A NP_001357681.1:p.Arg137His missense NM_001370753.1:c.399+2269G>A intron variant NM_001407364.1:c.410G>A NP_001394293.1:p.Arg137His missense NM_001407365.1:c.410G>A NP_001394294.1:p.Arg137His missense NM_001407366.1:c.410G>A NP_001394295.1:p.Arg137His missense NM_001407367.1:c.410G>A NP_001394296.1:p.Arg137His missense NM_001407368.1:c.410G>A NP_001394297.1:p.Arg137His missense NM_001407369.1:c.410G>A NP_001394298.1:p.Arg137His missense NM_001407370.1:c.410G>A NP_001394299.1:p.Arg137His missense NM_001407371.1:c.410G>A NP_001394300.1:p.Arg137His missense NM_001407372.1:c.410G>A NP_001394301.1:p.Arg137His missense NM_001407373.1:c.410G>A NP_001394302.1:p.Arg137His missense NM_001407374.1:c.410G>A NP_001394303.1:p.Arg137His missense NM_001407375.1:c.410G>A NP_001394304.1:p.Arg137His missense NM_001407376.1:c.410G>A NP_001394305.1:p.Arg137His missense NM_001407377.1:c.410G>A NP_001394306.1:p.Arg137His missense NM_001407378.1:c.410G>A NP_001394307.1:p.Arg137His missense NM_001407379.1:c.410G>A NP_001394308.1:p.Arg137His missense NC_000003.12:g.15644326G>A NC_000003.11:g.15685833G>A NG_008019.2:g.47975G>A NG_008019.3:g.47976G>A - Protein change
- R137H
- Other names
- R157H
- Canonical SPDI
- NC_000003.12:15644325:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00011
Trans-Omics for Precision Medicine (TOPMed) 0.00011
Exome Aggregation Consortium (ExAC) 0.00013
The Genome Aggregation Database (gnomAD) 0.00016
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
BTD | - | - |
GRCh38 GRCh37 |
667 | 753 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Mar 25, 2024 | RCV000021904.27 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Sep 16, 2022 | RCV000078072.21 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Oct 26, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000230012.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 7
Sex: mixed
|
|
Pathogenic
(Sep 16, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888018.3
First in ClinVar: Feb 15, 2018 Last updated: Jan 06, 2024 |
Comment:
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 … (more)
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. (less)
|
|
Pathogenic
(Mar 25, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004211386.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
Pathogenic
(Jan 08, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000329674.7
First in ClinVar: Dec 06, 2016 Last updated: Jul 29, 2023 |
Comment:
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, … (more)
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) (less)
|
|
Pathogenic
(Jan 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: yes
Allele origin:
germline
|
DASA
Accession: SCV002061179.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
Comment:
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; … (more)
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. (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Brazil
|
|
Pathogenic
(Dec 24, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV001193882.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 06, 2020 |
Comment:
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 … (more)
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. (less)
|
|
Pathogenic
(Jan 18, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000754949.4
First in ClinVar: Jan 06, 2018 Last updated: Feb 14, 2024 |
Comment:
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). … (more)
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. (less)
|
|
Pathogenic
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001460182.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
High frequency of biotinidase deficiency in Italian population identified by newborn screening. | Funghini S | Molecular genetics and metabolism reports | 2020 | PMID: 33312878 |
Evaluation of the efficiency of serum biotinidase activity as a newborn screening test in Turkey. | Ercan M | Journal of pediatric endocrinology & metabolism : JPEM | 2020 | PMID: 33189081 |
Twenty-seven mutations with three novel pathologenic variants causing biotinidase deficiency: a report of 203 patients from the southeastern part of Turkey. | Seker Yilmaz B | Journal of pediatric endocrinology & metabolism : JPEM | 2018 | PMID: 29353266 |
Neonatal screening for profound biotinidase deficiency in the Netherlands: consequences and considerations. | Wiltink RC | European journal of human genetics : EJHG | 2016 | PMID: 27329734 |
Biotinidase deficiency: Spectrum of molecular, enzymatic and clinical information from newborn screening Ontario, Canada (2007-2014). | Gannavarapu S | Molecular genetics and metabolism | 2015 | PMID: 26361991 |
Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth. | Loveday C | Human molecular genetics | 2015 | PMID: 25972378 |
Detection of biotinidase gene mutations in Turkish patients ascertained by newborn and family screening. | Karaca M | European journal of pediatrics | 2015 | PMID: 25754625 |
High incidence of partial biotinidase deficiency cases in newborns of Greek origin. | Thodi G | Gene | 2013 | PMID: 23644139 |
Increased incidence of profound biotinidase deficiency among Hispanic newborns in California. | Cowan TM | Molecular genetics and metabolism | 2012 | PMID: 22698809 |
Profound biotinidase deficiency: a rare disease among native Swedes. | Ohlsson A | Journal of inherited metabolic disease | 2010 | PMID: 20224900 |
Asymptomatic adults and older siblings with biotinidase deficiency ascertained by family studies of index cases. | Baykal T | Journal of inherited metabolic disease | 2005 | PMID: 16435182 |
Molecular characterisation of 34 patients with biotinidase deficiency ascertained by newborn screening and family investigation. | Mühl A | European journal of human genetics : EJHG | 2001 | PMID: 11313766 |
Novel mutations cause biotinidase deficiency in Turkish children. | Pomponio RJ | Journal of inherited metabolic disease | 2000 | PMID: 10801053 |
Mutations in the human biotinidase gene that cause profound biotinidase deficiency in symptomatic children: molecular, biochemical, and clinical analysis. | Pomponio RJ | Pediatric research | 1997 | PMID: 9396567 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BTD | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs146015592 ...
HelpRecord last updated Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.