This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with profound biotinidase deficiency (PMID: 9396567). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 24997). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. The observation of one or more missense substitutions at this codon (p.Glu112Gln, p.Glu112Lys) in affected individuals suggests that this may be a clinically significant residue (PMID: 9396567, 14707518). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 112 of the BTD protein (p.Glu112Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine.
ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.274G>C (p.Glu92Gln)
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.
(2)
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.
Likely pathogenic
2
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.274G>C (p.Glu92Gln)
Variation ID: 24997 Accession: VCV000024997.10
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p25.1 3: 15641932 (GRCh38) [ NCBI UCSC ] 3: 15683439 (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 Apr 4, 2013 Feb 14, 2024 Jul 19, 2018 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001370658.1:c.274G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.Glu92Gln missense NM_000060.4:c.334G>C NP_000051.1:p.Glu112Gln missense NM_001281723.4:c.274G>C NP_001268652.2:p.Glu92Gln missense NM_001281724.3:c.274G>C NP_001268653.2:p.Glu92Gln missense NM_001281725.3:c.274G>C NP_001268654.1:p.Glu92Gln missense NM_001281726.3:c.274G>C NP_001268655.2:p.Glu92Gln missense NM_001323582.2:c.274G>C NP_001310511.1:p.Glu92Gln missense NM_001370752.1:c.274G>C NP_001357681.1:p.Glu92Gln missense NM_001370753.1:c.274G>C NP_001357682.1:p.Glu92Gln missense NM_001407364.1:c.274G>C NP_001394293.1:p.Glu92Gln missense NM_001407365.1:c.274G>C NP_001394294.1:p.Glu92Gln missense NM_001407366.1:c.274G>C NP_001394295.1:p.Glu92Gln missense NM_001407367.1:c.274G>C NP_001394296.1:p.Glu92Gln missense NM_001407368.1:c.274G>C NP_001394297.1:p.Glu92Gln missense NM_001407369.1:c.274G>C NP_001394298.1:p.Glu92Gln missense NM_001407370.1:c.274G>C NP_001394299.1:p.Glu92Gln missense NM_001407371.1:c.274G>C NP_001394300.1:p.Glu92Gln missense NM_001407372.1:c.274G>C NP_001394301.1:p.Glu92Gln missense NM_001407373.1:c.274G>C NP_001394302.1:p.Glu92Gln missense NM_001407374.1:c.274G>C NP_001394303.1:p.Glu92Gln missense NM_001407375.1:c.274G>C NP_001394304.1:p.Glu92Gln missense NM_001407376.1:c.274G>C NP_001394305.1:p.Glu92Gln missense NM_001407377.1:c.274G>C NP_001394306.1:p.Glu92Gln missense NM_001407378.1:c.274G>C NP_001394307.1:p.Glu92Gln missense NM_001407379.1:c.274G>C NP_001394308.1:p.Glu92Gln missense NM_001407380.1:c.274G>C NP_001394309.1:p.Glu92Gln missense NM_001407381.1:c.337G>C NP_001394310.1:p.Glu113Gln missense NM_001407382.1:c.274G>C NP_001394311.1:p.Glu92Gln missense NM_001407383.1:c.274G>C NP_001394312.1:p.Glu92Gln missense NM_001407384.1:c.274G>C NP_001394313.1:p.Glu92Gln missense NM_001407386.1:c.274G>C NP_001394315.1:p.Glu92Gln missense NM_001407388.1:c.274G>C NP_001394317.1:p.Glu92Gln missense NM_001407390.1:c.274G>C NP_001394319.1:p.Glu92Gln missense NM_001407392.1:c.274G>C NP_001394321.1:p.Glu92Gln missense NM_001407394.1:c.274G>C NP_001394323.1:p.Glu92Gln missense NM_001407395.1:c.274G>C NP_001394324.1:p.Glu92Gln missense NM_001407396.1:c.274G>C NP_001394325.1:p.Glu92Gln missense NM_001407397.1:c.274G>C NP_001394326.1:p.Glu92Gln missense NM_001407398.1:c.274G>C NP_001394327.1:p.Glu92Gln missense NM_001407399.1:c.274G>C NP_001394328.1:p.Glu92Gln missense NM_001407400.1:c.274G>C NP_001394329.1:p.Glu92Gln missense NM_001407401.1:c.274G>C NP_001394330.1:p.Glu92Gln missense NC_000003.12:g.15641932G>C NC_000003.11:g.15683439G>C NG_008019.2:g.45581G>C - Protein change
- E92Q, E113Q
- Other names
- -
- Canonical SPDI
- NC_000003.12:15641931:G:C
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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.
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Trans-Omics for Precision Medicine (TOPMed) 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. |
|---|---|---|---|---|
| Likely pathogenic (1) |
criteria provided, single submitter
|
Jul 19, 2018 | RCV000021916.9 | |
| Likely pathogenic (1) |
criteria provided, single submitter
|
May 25, 2018 | RCV000759006.4 |
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
(May 25, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888015.2
First in ClinVar: Mar 14, 2019 Last updated: Jan 01, 2022 |
|
|
|
Likely pathogenic
(Jul 19, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000961511.4
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with¬†profound biotinidase deficiency¬†(PMID:¬†9396567). This finding is … (more)
This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with profound biotinidase deficiency (PMID: 9396567). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 24997). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. The observation of one or more missense substitutions at this codon (p.Glu112Gln, p.Glu112Lys) in affected individuals suggests that this may be a clinically significant residue (PMID: 9396567, 14707518). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 112 of the BTD protein (p.Glu112Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. (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:
This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with profound biotinidase deficiency (PMID: 9396567). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 24997). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. The observation of one or more missense substitutions at this codon (p.Glu112Gln, p.Glu112Lys) in affected individuals suggests that this may be a clinically significant residue (PMID: 9396567, 14707518). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 112 of the BTD protein (p.Glu112Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Neonatal screening for biotinidase deficiency in Hungary: clinical, biochemical and molecular studies. | László A | Journal of inherited metabolic disease | 2003 | PMID: 14707518 |
| Mutations in the human biotinidase gene that cause profound biotinidase deficiency in symptomatic children: molecular, biochemical, and clinical analysis. | Pomponio RJ | Pediatric research | 1997 | PMID: 9396567 |
Text-mined citations for rs397514352 ...
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.