ClinVar Genomic variation as it relates to human health
NM_000088.4(COL1A1):c.2644C>T (p.Arg882Ter)
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_000088.4(COL1A1):c.2644C>T (p.Arg882Ter)
Variation ID: 456753 Accession: VCV000456753.24
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.33 17: 50189702 (GRCh38) [ NCBI UCSC ] 17: 48267063 (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 Dec 26, 2017 Feb 20, 2024 Nov 19, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000088.4:c.2644C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000079.2:p.Arg882Ter nonsense NC_000017.11:g.50189702G>A NC_000017.10:g.48267063G>A NG_007400.1:g.16938C>T LRG_1:g.16938C>T LRG_1t1:c.2644C>T LRG_1p1:p.Arg882Ter - Protein change
- R882*
- Other names
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- Canonical SPDI
- NC_000017.11:50189701:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- functionally_normal Sequence Ontology [SO:0002219]
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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
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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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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COL1A1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2669 | 2865 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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 (1) |
criteria provided, single submitter
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Nov 19, 2023 | RCV000542101.8 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Nov 11, 2023 | RCV000578858.11 | |
not provided (1) |
no classification provided
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- | RCV001535522.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 1, 2020 | RCV002279330.3 |
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
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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
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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
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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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Pathogenic
(Jan 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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Osteogenesis imperfecta
Affected status: unknown
Allele origin:
germline
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Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002565164.1
First in ClinVar: Aug 29, 2022 Last updated: Aug 29, 2022 |
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Pathogenic
(Nov 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000680708.6
First in ClinVar: Feb 13, 2018 Last updated: Nov 25, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26627451, 31414283, 25533962, 21667357, 16786509, 22753364, 30614853, 27044453, 33939306, 33166682, 35476365, 15241796) (less)
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Pathogenic
(Jun 27, 2020)
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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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Revvity Omics, Revvity
Accession: SCV002017429.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Nov 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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Osteogenesis imperfecta type I
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000627209.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg882*) in the COL1A1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg882*) in the COL1A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL1A1 are known to be pathogenic (PMID: 7942841, 9295084, 9443882). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with osteogenesis imperfecta type I (PMID: 15241796, 21667357, 22753364, 26627451, 27044453). ClinVar contains an entry for this variant (Variation ID: 456753). For these reasons, this variant has been classified as Pathogenic. (less)
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not provided
(-)
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no classification provided
Method: phenotyping only
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Osteogenesis imperfecta
Ehlers-Danlos syndrome, arthrochalasia type
Affected status: unknown
Allele origin:
unknown
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GenomeConnect - Invitae Patient Insights Network
Accession: SCV001749485.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Comment:
Variant interpreted as Pathogenic and reported on 08-03-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report … (more)
Variant interpreted as Pathogenic and reported on 08-03-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Clinical Features:
Increased susceptibility to fractures (present)
Indication for testing: Diagnostic
Age: 30-39 years
Sex: male
Testing laboratory: Invitae
Date variant was reported to submitter: 2018-08-03
Testing laboratory interpretation: Pathogenic
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not provided
(-)
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no classification provided
Method: in vitro
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Not provided
Affected status: not applicable
Allele origin:
not applicable
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Human Development and Health, University of Southampton
Accession: SCV002106372.1
First in ClinVar: Mar 19, 2022 Last updated: Mar 19, 2022 |
Tissue: Blood
Method: RT-PCR
Result:
Normal splicing
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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functionally_normal
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Method citation(s):
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Human Development and Health, University of Southampton
Accession: SCV002106372.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Identification of two recurrent mutations of COL1A1 gene in Chinese Van der Hoeve syndrome patients. | Duan H | Acta oto-laryngologica | 2016 | PMID: 27044453 |
Genotype and phenotype analysis of Taiwanese patients with osteogenesis imperfecta. | Lin HY | Orphanet journal of rare diseases | 2015 | PMID: 26627451 |
Validation of a quantitative PCR-high-resolution melting protocol for simultaneous screening of COL1A1 and COL1A2 point mutations and large rearrangements: application for diagnosis of osteogenesis imperfecta. | Gentile FV | Human mutation | 2012 | PMID: 22753364 |
The identification of novel mutations in COL1A1, COL1A2, and LEPRE1 genes in Chinese patients with osteogenesis imperfecta. | Zhang ZL | Journal of bone and mineral metabolism | 2012 | PMID: 21667357 |
Lack of correlation between the type of COL1A1 or COL1A2 mutation and hearing loss in osteogenesis imperfecta patients. | Hartikka H | Human mutation | 2004 | PMID: 15241796 |
Analysis of the COL1A1 and COL1A2 genes by PCR amplification and scanning by conformation-sensitive gel electrophoresis identifies only COL1A1 mutations in 15 patients with osteogenesis imperfecta type I: identification of common sequences of null-allele mutations. | Körkkö J | American journal of human genetics | 1998 | PMID: 9443882 |
Ehlers-Danlos syndrome type VIIA and VIIB result from splice-junction mutations or genomic deletions that involve exon 6 in the COL1A1 and COL1A2 genes of type I collagen. | Byers PH | American journal of medical genetics | 1997 | PMID: 9295084 |
Osteogenesis imperfecta type I: molecular heterogeneity for COL1A1 null alleles of type I collagen. | Willing MC | American journal of human genetics | 1994 | PMID: 7942841 |
Text-mined citations for rs72653147 ...
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.