ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.805G>C (p.Ala269Pro)
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.805G>C (p.Ala269Pro)
Variation ID: 1459410 Accession: VCV001459410.5
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 3p25.1 3: 15644721 (GRCh38) [ NCBI UCSC ] 3: 15686228 (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 28, 2022 Feb 14, 2024 Jul 29, 2022 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001370658.1:c.805G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.Ala269Pro missense NM_000060.4:c.865G>C NP_000051.1:p.Ala289Pro missense NM_001281723.4:c.805G>C NP_001268652.2:p.Ala269Pro missense NM_001281724.3:c.805G>C NP_001268653.2:p.Ala269Pro missense NM_001281725.3:c.805G>C NP_001268654.1:p.Ala269Pro missense NM_001323582.2:c.805G>C NP_001310511.1:p.Ala269Pro missense NM_001370752.1:c.805G>C NP_001357681.1:p.Ala269Pro missense NM_001370753.1:c.399+2664G>C intron variant NM_001407364.1:c.805G>C NP_001394293.1:p.Ala269Pro missense NM_001407365.1:c.805G>C NP_001394294.1:p.Ala269Pro missense NM_001407366.1:c.805G>C NP_001394295.1:p.Ala269Pro missense NM_001407367.1:c.805G>C NP_001394296.1:p.Ala269Pro missense NM_001407368.1:c.805G>C NP_001394297.1:p.Ala269Pro missense NM_001407369.1:c.805G>C NP_001394298.1:p.Ala269Pro missense NM_001407370.1:c.805G>C NP_001394299.1:p.Ala269Pro missense NM_001407371.1:c.805G>C NP_001394300.1:p.Ala269Pro missense NM_001407372.1:c.805G>C NP_001394301.1:p.Ala269Pro missense NM_001407373.1:c.805G>C NP_001394302.1:p.Ala269Pro missense NM_001407374.1:c.805G>C NP_001394303.1:p.Ala269Pro missense NM_001407375.1:c.805G>C NP_001394304.1:p.Ala269Pro missense NM_001407376.1:c.805G>C NP_001394305.1:p.Ala269Pro missense NM_001407377.1:c.805G>C NP_001394306.1:p.Ala269Pro missense NM_001407378.1:c.805G>C NP_001394307.1:p.Ala269Pro missense NM_001407379.1:c.805G>C NP_001394308.1:p.Ala269Pro missense NC_000003.12:g.15644721G>C NC_000003.11:g.15686228G>C NG_008019.2:g.48370G>C NG_008019.3:g.48371G>C - Protein change
- A269P
- Other names
- A289P
- Canonical SPDI
- NC_000003.12:15644720:G:C
-
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 |
645 | 705 |
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 (1) |
criteria provided, single submitter
|
Jul 29, 2022 | RCV001975221.11 |
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 29, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002243818.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact … (more)
Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1459410). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 10400129, 26810761, 27657684; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 289 of the BTD protein (p.Ala289Pro). For these reasons, this variant has been classified as Pathogenic. (less)
|
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 |
---|---|---|---|---|
Successful outcomes of older adolescents and adults with profound biotinidase deficiency identified by newborn screening. | Wolf B | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 27657684 |
Forty-eight novel mutations causing biotinidase deficiency. | Procter M | Molecular genetics and metabolism | 2016 | PMID: 26810761 |
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 |
Text-mined citations for rs397514334 ...
HelpRecord last updated Apr 15, 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.