ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.218A>G (p.Tyr73Cys)
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
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NM_001370658.1(BTD):c.218A>G (p.Tyr73Cys)
Variation ID: 24993 Accession: VCV000024993.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p25.1 3: 15635657 (GRCh38) [ NCBI UCSC ] 3: 15677164 (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 20, 2024 Jan 5, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370658.1:c.218A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.Tyr73Cys missense NM_000060.4:c.278A>G NP_000051.1:p.Tyr93Cys missense NM_001281723.4:c.218A>G NP_001268652.2:p.Tyr73Cys missense NM_001281724.3:c.218A>G NP_001268653.2:p.Tyr73Cys missense NM_001281725.3:c.218A>G NP_001268654.1:p.Tyr73Cys missense NM_001281726.3:c.218A>G NP_001268655.2:p.Tyr73Cys missense NM_001323582.2:c.218A>G NP_001310511.1:p.Tyr73Cys missense NM_001370752.1:c.218A>G NP_001357681.1:p.Tyr73Cys missense NM_001370753.1:c.218A>G NP_001357682.1:p.Tyr73Cys missense NM_001407364.1:c.218A>G NP_001394293.1:p.Tyr73Cys missense NM_001407365.1:c.218A>G NP_001394294.1:p.Tyr73Cys missense NM_001407366.1:c.218A>G NP_001394295.1:p.Tyr73Cys missense NM_001407367.1:c.218A>G NP_001394296.1:p.Tyr73Cys missense NM_001407368.1:c.218A>G NP_001394297.1:p.Tyr73Cys missense NM_001407369.1:c.218A>G NP_001394298.1:p.Tyr73Cys missense NM_001407370.1:c.218A>G NP_001394299.1:p.Tyr73Cys missense NM_001407371.1:c.218A>G NP_001394300.1:p.Tyr73Cys missense NM_001407372.1:c.218A>G NP_001394301.1:p.Tyr73Cys missense NM_001407373.1:c.218A>G NP_001394302.1:p.Tyr73Cys missense NM_001407374.1:c.218A>G NP_001394303.1:p.Tyr73Cys missense NM_001407375.1:c.218A>G NP_001394304.1:p.Tyr73Cys missense NM_001407376.1:c.218A>G NP_001394305.1:p.Tyr73Cys missense NM_001407377.1:c.218A>G NP_001394306.1:p.Tyr73Cys missense NM_001407378.1:c.218A>G NP_001394307.1:p.Tyr73Cys missense NM_001407379.1:c.218A>G NP_001394308.1:p.Tyr73Cys missense NM_001407380.1:c.218A>G NP_001394309.1:p.Tyr73Cys missense NM_001407381.1:c.218A>G NP_001394310.1:p.Tyr73Cys missense NM_001407382.1:c.218A>G NP_001394311.1:p.Tyr73Cys missense NM_001407383.1:c.218A>G NP_001394312.1:p.Tyr73Cys missense NM_001407384.1:c.218A>G NP_001394313.1:p.Tyr73Cys missense NM_001407386.1:c.218A>G NP_001394315.1:p.Tyr73Cys missense NM_001407388.1:c.218A>G NP_001394317.1:p.Tyr73Cys missense NM_001407390.1:c.218A>G NP_001394319.1:p.Tyr73Cys missense NM_001407392.1:c.218A>G NP_001394321.1:p.Tyr73Cys missense NM_001407394.1:c.218A>G NP_001394323.1:p.Tyr73Cys missense NM_001407395.1:c.218A>G NP_001394324.1:p.Tyr73Cys missense NM_001407396.1:c.218A>G NP_001394325.1:p.Tyr73Cys missense NM_001407397.1:c.218A>G NP_001394326.1:p.Tyr73Cys missense NM_001407398.1:c.218A>G NP_001394327.1:p.Tyr73Cys missense NM_001407399.1:c.218A>G NP_001394328.1:p.Tyr73Cys missense NM_001407400.1:c.218A>G NP_001394329.1:p.Tyr73Cys missense NM_001407401.1:c.218A>G NP_001394330.1:p.Tyr73Cys missense NC_000003.12:g.15635657A>G NC_000003.11:g.15677164A>G NG_008019.2:g.39306A>G - Protein change
- Y73C
- Other names
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- Canonical SPDI
- NC_000003.12:15635656:A:G
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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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00000
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 | ||
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HI score
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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. |
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jan 5, 2024 | RCV000021911.11 |
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. |
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Likely pathogenic
(Mar 28, 2018)
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criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000798916.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
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Pathogenic
(Oct 03, 2023)
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criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004211418.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jan 05, 2024)
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criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001590142.4
First in ClinVar: May 10, 2021 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 93 of the BTD protein … (more)
This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 93 of the BTD protein (p.Tyr93Cys). This variant is present in population databases (rs397514348, gnomAD 0.003%). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 12359137, 25144890, 26810761; Invitae). ClinVar contains an entry for this variant (Variation ID: 24993). 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)
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Pathogenic
(Sep 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004099989.1
First in ClinVar: Nov 04, 2023 Last updated: Nov 04, 2023 |
Comment:
Variant summary: BTD c.218A>G (p.Tyr73Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: BTD c.218A>G (p.Tyr73Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251380 control chromosomes (gnomAD). c.218A>G (also known as c.278A>G/p.Y93C) has been reported in the literature in multiple individuals affected with Biotinidase Deficiency (examples: Wolf_2002, Jay_2016, Procter_2016, Maguolo_2021, Akgun_2021). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 34448386, 25144890, 34136440, 26810761, 12359137). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jun 10, 2021)
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no assertion criteria provided
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002081547.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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 |
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Clinical, biochemical and genotypical characteristics in biotinidase deficiency. | Akgun A | Journal of pediatric endocrinology & metabolism : JPEM | 2021 | PMID: 34448386 |
Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy. | Maguolo A | Frontiers in pediatrics | 2021 | PMID: 34136440 |
Biotinidase deficiency: Genotype-biochemical phenotype association in Brazilian patients. | Borsatto T | PloS one | 2017 | PMID: 28498829 |
Forty-eight novel mutations causing biotinidase deficiency. | Procter M | Molecular genetics and metabolism | 2016 | PMID: 26810761 |
Detection of biotinidase gene mutations in Turkish patients ascertained by newborn and family screening. | Karaca M | European journal of pediatrics | 2015 | PMID: 25754625 |
Outcomes of individuals with profound and partial biotinidase deficiency ascertained by newborn screening in Michigan over 25 years. | Jay AM | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25144890 |
Seventeen novel mutations that cause profound biotinidase deficiency. | Wolf B | Molecular genetics and metabolism | 2002 | PMID: 12359137 |
Text-mined citations for rs397514348 ...
HelpRecord last updated Feb 28, 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.