Variant summary: BTD c.187_195delTTGGAGCTC (p.Leu63_Leu65del) results in an in-frame deletion that is predicted to remove three amino acids from the encoded protein. The variant was absent in 251408 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.187_195delTTGGAGCTC has been reported in the literature in at least one individual affected with Biotinidase Deficiency (e.g., Pomponio_1997, Norrgard_1999). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.187_195del (p.Leu63_Leu65del)
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.
Uncertain significance
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001370658.1(BTD):c.187_195del (p.Leu63_Leu65del)
Variation ID: 1365614 Accession: VCV001365614.5
- Type and length
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Deletion, 9 bp
- Location
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Cytogenetic: 3p25.1 3: 15635625-15635633 (GRCh38) [ NCBI UCSC ] 3: 15677132-15677140 (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 Mar 28, 2022 Feb 14, 2024 Feb 8, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001370658.1:c.187_195del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.Leu63_Leu65del inframe deletion NM_001370658.1:c.187_195delTTGGAGCTC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
inframe deletion NM_001281723.4:c.187_195del NP_001268652.2:p.Leu63_Leu65del inframe deletion NM_001281724.3:c.187_195del NP_001268653.2:p.Leu63_Leu65del inframe deletion NM_001281725.3:c.187_195del NP_001268654.1:p.Leu63_Leu65del inframe deletion NM_001281726.3:c.187_195del NP_001268655.2:p.Leu63_Leu65del inframe deletion NM_001323582.2:c.187_195del NP_001310511.1:p.Leu63_Leu65del inframe deletion NM_001370752.1:c.187_195del NP_001357681.1:p.Leu63_Leu65del inframe deletion NM_001370753.1:c.187_195del NP_001357682.1:p.Leu63_Leu65del inframe deletion NM_001407364.1:c.187_195del NP_001394293.1:p.Leu63_Leu65del inframe deletion NM_001407365.1:c.187_195del NP_001394294.1:p.Leu63_Leu65del inframe deletion NM_001407366.1:c.187_195del NP_001394295.1:p.Leu63_Leu65del inframe deletion NM_001407367.1:c.187_195del NP_001394296.1:p.Leu63_Leu65del inframe deletion NM_001407368.1:c.187_195del NP_001394297.1:p.Leu63_Leu65del inframe deletion NM_001407369.1:c.187_195del NP_001394298.1:p.Leu63_Leu65del inframe deletion NM_001407370.1:c.187_195del NP_001394299.1:p.Leu63_Leu65del inframe deletion NM_001407371.1:c.187_195del NP_001394300.1:p.Leu63_Leu65del inframe deletion NM_001407372.1:c.187_195del NP_001394301.1:p.Leu63_Leu65del inframe deletion NM_001407373.1:c.187_195del NP_001394302.1:p.Leu63_Leu65del inframe deletion NM_001407374.1:c.187_195del NP_001394303.1:p.Leu63_Leu65del inframe deletion NM_001407375.1:c.187_195del NP_001394304.1:p.Leu63_Leu65del inframe deletion NM_001407376.1:c.187_195del NP_001394305.1:p.Leu63_Leu65del inframe deletion NM_001407377.1:c.187_195del NP_001394306.1:p.Leu63_Leu65del inframe deletion NM_001407378.1:c.187_195del NP_001394307.1:p.Leu63_Leu65del inframe deletion NM_001407379.1:c.187_195del NP_001394308.1:p.Leu63_Leu65del inframe deletion NM_001407380.1:c.187_195del NP_001394309.1:p.Leu63_Leu65del inframe deletion NM_001407381.1:c.187_195del NP_001394310.1:p.Leu63_Leu65del inframe deletion NM_001407382.1:c.187_195del NP_001394311.1:p.Leu63_Leu65del inframe deletion NM_001407383.1:c.187_195del NP_001394312.1:p.Leu63_Leu65del inframe deletion NM_001407384.1:c.187_195del NP_001394313.1:p.Leu63_Leu65del inframe deletion NM_001407386.1:c.187_195del NP_001394315.1:p.Leu63_Leu65del inframe deletion NM_001407388.1:c.187_195del NP_001394317.1:p.Leu63_Leu65del inframe deletion NM_001407390.1:c.187_195del NP_001394319.1:p.Leu63_Leu65del inframe deletion NM_001407392.1:c.187_195del NP_001394321.1:p.Leu63_Leu65del inframe deletion NM_001407394.1:c.187_195del NP_001394323.1:p.Leu63_Leu65del inframe deletion NM_001407395.1:c.187_195del NP_001394324.1:p.Leu63_Leu65del inframe deletion NM_001407396.1:c.187_195del NP_001394325.1:p.Leu63_Leu65del inframe deletion NM_001407397.1:c.187_195del NP_001394326.1:p.Leu63_Leu65del inframe deletion NM_001407398.1:c.187_195del NP_001394327.1:p.Leu63_Leu65del inframe deletion NM_001407399.1:c.187_195del NP_001394328.1:p.Leu63_Leu65del inframe deletion NM_001407400.1:c.187_195del NP_001394329.1:p.Leu63_Leu65del inframe deletion NM_001407401.1:c.187_195del NP_001394330.1:p.Leu63_Leu65del inframe deletion NC_000003.12:g.15635626_15635634del NC_000003.11:g.15677133_15677141del NG_008019.2:g.39275_39283del NG_008019.3:g.39276_39284del - Protein change
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- Other names
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L85del
- Canonical SPDI
- NC_000003.12:15635624:CTTGGAGCTC: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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- 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 |
669 | 755 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
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Feb 22, 2021 | RCV001929892.5 | |
| Uncertain significance (1) |
criteria provided, single submitter
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Feb 8, 2023 | RCV003155434.1 |
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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|---|---|---|---|---|---|
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Uncertain significance
(Feb 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003844449.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
Variant summary: BTD c.187_195delTTGGAGCTC (p.Leu63_Leu65del) results in an in-frame deletion that is predicted to remove three amino acids from the encoded protein. The variant was … (more)
Variant summary: BTD c.187_195delTTGGAGCTC (p.Leu63_Leu65del) results in an in-frame deletion that is predicted to remove three amino acids from the encoded protein. The variant was absent in 251408 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.187_195delTTGGAGCTC has been reported in the literature in at least one individual affected with Biotinidase Deficiency (e.g., Pomponio_1997, Norrgard_1999). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
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Uncertain significance
(Feb 22, 2021)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002130589.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This variant, c.247_255del, results in the deletion of 3 amino acid(s) of the BTD protein (p.Leu83_Leu85del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.247_255del, results in the deletion of 3 amino acid(s) of the BTD protein (p.Leu83_Leu85del), but otherwise preserves the integrity of the reading frame. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts a region of the protein in which other variant(s) (p.Leu83Ser) have been observed in individuals with BTD-related conditions (PMID: 20224900). This suggests that this may be a clinically significant region of the BTD protein. This variant has been observed in individual(s) with biotinidase deficiency (PMID: 9396567). ClinVar contains an entry for this variant (Variation ID: 587750). This variant is not present in population databases (ExAC no frequency). (less)
|
Comment:
Comment:
This variant, c.247_255del, results in the deletion of 3 amino acid(s) of the BTD protein (p.Leu83_Leu85del), but otherwise preserves the integrity of the reading frame. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts a region of the protein in which other variant(s) (p.Leu83Ser) have been observed in individuals with BTD-related conditions (PMID: 20224900). This suggests that this may be a clinically significant region of the BTD protein. This variant has been observed in individual(s) with biotinidase deficiency (PMID: 9396567). ClinVar contains an entry for this variant (Variation ID: 587750). This variant is not present in population databases (ExAC no frequency).
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:
Variant summary: BTD c.187_195delTTGGAGCTC (p.Leu63_Leu65del) results in an in-frame deletion that is predicted to remove three amino acids from the encoded protein. The variant was absent in 251408 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.187_195delTTGGAGCTC has been reported in the literature in at least one individual affected with Biotinidase Deficiency (e.g., Pomponio_1997, Norrgard_1999). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Comment:
This variant, c.247_255del, results in the deletion of 3 amino acid(s) of the BTD protein (p.Leu83_Leu85del), but otherwise preserves the integrity of the reading frame. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts a region of the protein in which other variant(s) (p.Leu83Ser) have been observed in individuals with BTD-related conditions (PMID: 20224900). This suggests that this may be a clinically significant region of the BTD protein. This variant has been observed in individual(s) with biotinidase deficiency (PMID: 9396567). ClinVar contains an entry for this variant (Variation ID: 587750). This variant is not present in population databases (ExAC no frequency).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Profound biotinidase deficiency: a rare disease among native Swedes. | Ohlsson A | Journal of inherited metabolic disease | 2010 | PMID: 20224900 |
| 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 |
| 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 rs397514346 ...
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.