ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.674G>A (p.Cys225Tyr)
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.674G>A (p.Cys225Tyr)
Variation ID: 38281 Accession: VCV000038281.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p25.1 3: 15644590 (GRCh38) [ NCBI UCSC ] 3: 15686097 (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 May 30, 2018 Feb 14, 2024 Oct 17, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370658.1:c.674G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.Cys225Tyr missense NM_000060.4:c.734G>A NP_000051.1:p.Cys245Tyr missense NM_001281723.4:c.674G>A NP_001268652.2:p.Cys225Tyr missense NM_001281724.3:c.674G>A NP_001268653.2:p.Cys225Tyr missense NM_001281725.3:c.674G>A NP_001268654.1:p.Cys225Tyr missense NM_001323582.2:c.674G>A NP_001310511.1:p.Cys225Tyr missense NM_001370752.1:c.674G>A NP_001357681.1:p.Cys225Tyr missense NM_001370753.1:c.399+2533G>A intron variant NM_001407364.1:c.674G>A NP_001394293.1:p.Cys225Tyr missense NM_001407365.1:c.674G>A NP_001394294.1:p.Cys225Tyr missense NM_001407366.1:c.674G>A NP_001394295.1:p.Cys225Tyr missense NM_001407367.1:c.674G>A NP_001394296.1:p.Cys225Tyr missense NM_001407368.1:c.674G>A NP_001394297.1:p.Cys225Tyr missense NM_001407369.1:c.674G>A NP_001394298.1:p.Cys225Tyr missense NM_001407370.1:c.674G>A NP_001394299.1:p.Cys225Tyr missense NM_001407371.1:c.674G>A NP_001394300.1:p.Cys225Tyr missense NM_001407372.1:c.674G>A NP_001394301.1:p.Cys225Tyr missense NM_001407373.1:c.674G>A NP_001394302.1:p.Cys225Tyr missense NM_001407374.1:c.674G>A NP_001394303.1:p.Cys225Tyr missense NM_001407375.1:c.674G>A NP_001394304.1:p.Cys225Tyr missense NM_001407376.1:c.674G>A NP_001394305.1:p.Cys225Tyr missense NM_001407377.1:c.674G>A NP_001394306.1:p.Cys225Tyr missense NM_001407378.1:c.674G>A NP_001394307.1:p.Cys225Tyr missense NM_001407379.1:c.674G>A NP_001394308.1:p.Cys225Tyr missense NC_000003.12:g.15644590G>A NC_000003.11:g.15686097G>A NG_008019.2:g.48239G>A NG_008019.3:g.48240G>A - Protein change
- C225Y
- Other names
- C245Y
- Canonical SPDI
- NC_000003.12:15644589:G:A
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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.
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
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
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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
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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 | - |
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
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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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Oct 17, 2023 | RCV000021959.30 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Mar 17, 2015 | RCV000724643.12 |
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 17, 2015)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000230003.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Oct 12, 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: SCV004211407.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Aug 05, 2019)
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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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Revvity Omics, Revvity
Accession: SCV002017996.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Likely pathogenic
(Feb 22, 2022)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002506313.2
First in ClinVar: May 07, 2022 Last updated: Dec 24, 2022 |
Comment:
The BTD c.734G>A; p.Cys245Tyr variant (rs397507175) is reported in the literature in multiple individuals affected with profound biotinidase deficiency usually (Jay 2015, Porta 2017, Wolf … (more)
The BTD c.734G>A; p.Cys245Tyr variant (rs397507175) is reported in the literature in multiple individuals affected with profound biotinidase deficiency usually (Jay 2015, Porta 2017, Wolf 2005). This variant is reported in ClinVar (Variation ID: 38281) and is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The cysteine at codon 245 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.924). Based on available information, this variant is considered to be likely pathogenic. References: Jay AM et al. Outcomes of individuals with profound and partial biotinidase deficiency ascertained by newborn screening in Michigan over 25 years. Genet Med. 2015 Mar;17(3):205-9. PMID: 25144890. Porta F et al. Neonatal screening for biotinidase deficiency: A 30-year single center experience. Mol Genet Metab Rep. 2017 Sep 20;13:80-82. PMID: 28971021. Wolf B et al. Biotinidase deficiency: novel mutations and their biochemical and clinical correlates. Hum Mutat. 2005 Apr;25(4):413. PMID: 15776412. (less)
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Pathogenic
(Oct 17, 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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Invitae
Accession: SCV000817625.4
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 245 of the BTD protein … (more)
This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 245 of the BTD protein (p.Cys245Tyr). This variant is present in population databases (rs397507175, gnomAD 0.002%). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 15776412, 28971021). 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: 38281). 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. For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Mar 02, 2019)
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no assertion criteria provided
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000797130.2
First in ClinVar: May 30, 2018 Last updated: Dec 23, 2019 |
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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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Neonatal screening for biotinidase deficiency: A 30-year single center experience. | Porta F | Molecular genetics and metabolism reports | 2017 | PMID: 28971021 |
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 |
Biotinidase deficiency: novel mutations and their biochemical and clinical correlates. | Wolf B | Human mutation | 2005 | PMID: 15776412 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BTD | - | - | - | - |
Text-mined citations for rs397507175 ...
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.