For these reasons, this variant has been classified as Pathogenic. 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: 25083). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 18645204, 21907891). This variant is present in population databases (rs397514418, gnomAD 0.003%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 447 of the BTD protein (p.His447Tyr).
ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.1279C>T (p.His427Tyr)
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.
(3)
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
3
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.1279C>T (p.His427Tyr)
Variation ID: 25083 Accession: VCV000025083.6
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p25.1 3: 15645195 (GRCh38) [ NCBI UCSC ] 3: 15686702 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Apr 4, 2013 Feb 14, 2024 Apr 17, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001370658.1:c.1279C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.His427Tyr missense NM_000060.4:c.1339C>T NP_000051.1:p.His447Tyr missense NM_001281723.4:c.1279C>T NP_001268652.2:p.His427Tyr missense NM_001281724.3:c.1279C>T NP_001268653.2:p.His427Tyr missense NM_001281725.3:c.1279C>T NP_001268654.1:p.His427Tyr missense NM_001323582.2:c.1279C>T NP_001310511.1:p.His427Tyr missense NM_001370752.1:c.1015+264C>T intron variant NM_001370753.1:c.399+3138C>T intron variant NM_001407364.1:c.1279C>T NP_001394293.1:p.His427Tyr missense NM_001407365.1:c.1279C>T NP_001394294.1:p.His427Tyr missense NM_001407366.1:c.1279C>T NP_001394295.1:p.His427Tyr missense NM_001407367.1:c.1279C>T NP_001394296.1:p.His427Tyr missense NM_001407368.1:c.1279C>T NP_001394297.1:p.His427Tyr missense NM_001407369.1:c.1279C>T NP_001394298.1:p.His427Tyr missense NM_001407370.1:c.1279C>T NP_001394299.1:p.His427Tyr missense NM_001407371.1:c.1279C>T NP_001394300.1:p.His427Tyr missense NM_001407372.1:c.1279C>T NP_001394301.1:p.His427Tyr missense NM_001407373.1:c.1279C>T NP_001394302.1:p.His427Tyr missense NM_001407374.1:c.1279C>T NP_001394303.1:p.His427Tyr missense NM_001407375.1:c.1279C>T NP_001394304.1:p.His427Tyr missense NM_001407376.1:c.1279C>T NP_001394305.1:p.His427Tyr missense NM_001407377.1:c.1279C>T NP_001394306.1:p.His427Tyr missense NM_001407378.1:c.1279C>T NP_001394307.1:p.His427Tyr missense NC_000003.12:g.15645195C>T NC_000003.11:g.15686702C>T NG_008019.2:g.48844C>T NG_008019.3:g.48845C>T - Protein change
- H427Y
- Other names
- -
- Canonical SPDI
- NC_000003.12:15645194:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
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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.
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The Genome Aggregation Database (gnomAD), exomes 0.00000
- 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 |
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/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Apr 17, 2023 | RCV000022008.7 |
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. |
|
|---|---|---|---|---|---|
|
Likely pathogenic
(Jul 19, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000792876.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
|
|
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Pathogenic
(-)
|
criteria provided, single submitter
Method: research
|
Biotinidase deficiency
Affected status: yes
Allele origin:
inherited
|
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
Accession: SCV002053929.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
|
|
|
Pathogenic
(Apr 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004293426.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, … (more)
For these reasons, this variant has been classified as Pathogenic. 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: 25083). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 18645204, 21907891). This variant is present in population databases (rs397514418, gnomAD 0.003%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 447 of the BTD protein (p.His447Tyr). (less)
|
Comment:
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:
For these reasons, this variant has been classified as Pathogenic. 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: 25083). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 18645204, 21907891). This variant is present in population databases (rs397514418, gnomAD 0.003%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 447 of the BTD protein (p.His447Tyr).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
| Detection of biotinidase gene mutations in Turkish patients ascertained by newborn and family screening. | Karaca M | European journal of pediatrics | 2015 | PMID: 25754625 |
| Biotinidase deficiency presenting as recurrent myelopathy in a 7-year-old boy and a review of the literature. | Raha S | Pediatric neurology | 2011 | PMID: 21907891 |
| Analysis of mutations causing biotinidase deficiency. | Pindolia K | Human mutation | 2010 | PMID: 20556795 |
| Profound biotinidase deficiency in a child with predominantly spinal cord disease. | Chedrawi AK | Journal of child neurology | 2008 | PMID: 18645204 |
Text-mined citations for rs397514418 ...
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 Sep 29, 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.