This sequence change creates a premature translational stop signal (p.Trp409Cysfs*91) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 135 amino acid(s) of the BTD protein. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This premature translational stop signal has been observed in individual(s) with biotinidase deficiency (PMID: 8894703). This variant disrupts a region of the BTD protein in which other variant(s) (p.Leu498Phefs*13) have been determined to be pathogenic (PMID: 17382128, 19728141, 29359854). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.1167_1181delinsTTCCAATGGCC (p.Trp389fs)
Germline
Classification
Help
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.
(6)
Help
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.
Pathogenic/Likely pathogenic
6
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001370658.1(BTD):c.1167_1181delinsTTCCAATGGCC (p.Trp389fs)
Variation ID: 188805 Accession: VCV000188805.15
- Type and length
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Indel, 15 bp
- Location
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Cytogenetic: 3p25.1 3: 15645083-15645097 (GRCh38) [ NCBI UCSC ] 3: 15686590-15686604 (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 Mar 29, 2015 Jun 17, 2024 Mar 9, 2024 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- W389fs
- Other names
- -
- Canonical SPDI
- NC_000003.12:15645082:GGGAAAGGAAGGCTA:TTCCAATGGCC
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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.
- -
- Links
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 |
671 | 759 | |
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/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Mar 9, 2024 | RCV000169138.11 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Aug 10, 2021 | RCV000728443.6 |
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
(Jul 25, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000856021.1
First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018 |
Number of individuals with the variant: 1
Zygosity: Single Heterozygote
Sex: mixed
|
|
|
Likely pathogenic
(May 28, 2014)
|
criteria provided, single submitter
Method: literature only
|
Biotinidase deficiency
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000220356.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
|
|
|
Pathogenic
(Nov 21, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001421739.3
First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Trp409Cysfs*91) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Trp409Cysfs*91) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 135 amino acid(s) of the BTD protein. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This premature translational stop signal has been observed in individual(s) with biotinidase deficiency (PMID: 8894703). This variant disrupts a region of the BTD protein in which other variant(s) (p.Leu498Phefs*13) have been determined to be pathogenic (PMID: 17382128, 19728141, 29359854). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Aug 10, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV002774330.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
Comment:
This frameshift variant causes the premature termination of BTD protein synthesis. In addition, it has been reported in a child with biotinidase deficiency in the … (more)
This frameshift variant causes the premature termination of BTD protein synthesis. In addition, it has been reported in a child with biotinidase deficiency in the published literature (PMID: 8894703 (1996)). Based on the available information, this variant is classified as pathogenic. (less)
|
|
|
Pathogenic
(Mar 09, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004211415.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Oct 01, 1996)
|
no assertion criteria provided
Method: literature only
|
BIOTINIDASE DEFICIENCY
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000022131.2
First in ClinVar: Apr 04, 2013 Last updated: Aug 16, 2015 |
Comment on evidence:
In a child with profound biotinidase deficiency (253260), Pomponio et al. (1996) identified homozygosity for a 15-bp deletion/11-bp insertion mutation within exon D (nucleotides 1059-1359 … (more)
In a child with profound biotinidase deficiency (253260), Pomponio et al. (1996) identified homozygosity for a 15-bp deletion/11-bp insertion mutation within exon D (nucleotides 1059-1359 of the sequence reported by Cole et al. (1994)) of the BTD gene. The mutation resulted in a frameshift predicted to terminate the polypeptide prematurely. The authors proposed 2 possible mechanisms to account for this mutation, both of which involved formation of a quasipalindromic structure in the replicating DNA strands. (less)
|
Comment:
Comment:
This frameshift variant causes the premature termination of BTD protein synthesis. In addition, it has been reported in a child with biotinidase deficiency in the published literature (PMID: 8894703 (1996)). Based on the available information, this variant is classified as pathogenic.
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. |
Comment:
This sequence change creates a premature translational stop signal (p.Trp409Cysfs*91) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 135 amino acid(s) of the BTD protein. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This premature translational stop signal has been observed in individual(s) with biotinidase deficiency (PMID: 8894703). This variant disrupts a region of the BTD protein in which other variant(s) (p.Leu498Phefs*13) have been determined to be pathogenic (PMID: 17382128, 19728141, 29359854). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Comment:
This frameshift variant causes the premature termination of BTD protein synthesis. In addition, it has been reported in a child with biotinidase deficiency in the published literature (PMID: 8894703 (1996)). Based on the available information, this variant is classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Clinical features, BTD gene mutations, and their functional studies of eight symptomatic patients with biotinidase deficiency from Southern China. | Liu Z | American journal of medical genetics. Part A | 2018 | PMID: 29359854 |
| Diagnosis, treatment, follow-up and gene mutation analysis in four Chinese children with biotinidase deficiency. | Ye J | Journal of inherited metabolic disease | 2009 | PMID: 19728141 |
| Hearing loss in biotinidase deficiency: genotype-phenotype correlation. | Sivri HS | The Journal of pediatrics | 2007 | PMID: 17382128 |
| Mutations in BTD causing biotinidase deficiency. | Hymes J | Human mutation | 2001 | PMID: 11668630 |
| Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children. | Norrgard KJ | Pediatric research | 1999 | PMID: 10400129 |
| Deletion/insertion mutation that causes biotinidase deficiency may result from the formation of a quasipalindromic structure. | Pomponio RJ | Human molecular genetics | 1996 | PMID: 8894703 |
| Human serum biotinidase. cDNA cloning, sequence, and characterization. | Cole H | The Journal of biological chemistry | 1994 | PMID: 7509806 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BTD | - | - | - | - |
Text-mined citations for rs672601248 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Jan 04, 2025
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.