ClinVar Genomic variation as it relates to human health
NM_000088.4(COL1A1):c.579del (p.Gly194fs)
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.579del (p.Gly194fs)
Variation ID: 35925 Accession: VCV000035925.19
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 17q21.33 17: 50198170 (GRCh38) [ NCBI UCSC ] 17: 48275531 (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 Sep 16, 2024 Jun 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000088.4:c.579del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000079.2:p.Gly194fs frameshift NM_000088.3:c.579delT NC_000017.11:g.50198170del NC_000017.10:g.48275531del NG_007400.1:g.8470del LRG_1:g.8470del LRG_1t1:c.579del LRG_1p1:p.Gly194fs - Protein change
- G194fs
- Other names
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- Canonical SPDI
- NC_000017.11:50198169: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
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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
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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COL1A1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2736 | 2937 |
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 (2) |
criteria provided, multiple submitters, no conflicts
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Dec 1, 2019 | RCV000029580.5 | |
Pathogenic (2) |
criteria provided, single submitter
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Dec 10, 2023 | RCV000490677.6 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jun 25, 2024 | RCV000627432.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 14, 2021 | RCV001526512.2 |
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
(Aug 18, 2011)
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criteria provided, single submitter
Method: curation, clinical testing
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Osteogenesis Imperfecta
(autosomal dominant)
Affected status: yes, unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000052232.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 08, 2022 |
Comment:
Converted during submission to Likely pathogenic.
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
Observation 3:
Tissue: Blood
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Pathogenic
(Dec 01, 2019)
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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: SCV002564741.1
First in ClinVar: Aug 29, 2022 Last updated: Aug 29, 2022 |
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Pathogenic
(Dec 10, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001379847.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gly194Valfs*71) 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.Gly194Valfs*71) 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 individual(s) with osteogenesis imperfecta (PMID: 16879195, 27510842). ClinVar contains an entry for this variant (Variation ID: 35925). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jul 13, 2022)
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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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Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005197558.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
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Pathogenic
(Jun 25, 2024)
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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: SCV000748431.8
First in ClinVar: May 21, 2018 Last updated: Sep 16, 2024 |
Comment:
Frameshift 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 … (more)
Frameshift 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: 36709916, 37334733, 35909573, 34902613, 36951356, 25944380, 19358256, 22679784, 23195995, 27510842, 26627451, 16879195, 21884818, 32034735, 28528406, 29502568, 32166892, 21667357) (less)
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Pathogenic
(Jun 14, 2021)
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criteria provided, single submitter
Method: not provided
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Osteoporosis
Affected status: yes
Allele origin:
germline
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Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin
Additional submitter:
CUBI - Core Unit Bioinformatics, Berlin Institute of Health
Accession: SCV001736932.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
Sex: male
Tissue: Blood
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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OI type I
Affected status: yes
Allele origin:
maternal,
paternal
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Department of Medical Sciences, Uppsala University
Additional submitter:
Department of Dental Medicine, Karolinska Institutet
Accession: SCV000574581.1
First in ClinVar: Jun 10, 2017 Last updated: Jun 10, 2017 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
Observation 3:
Number of individuals with the variant: 1
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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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Tooth agenesis in osteogenesis imperfecta related to mutations in the collagen type I genes. | Malmgren B | Oral diseases | 2017 | PMID: 27510842 |
Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta. | Lindahl K | European journal of human genetics : EJHG | 2015 | PMID: 25944380 |
Audiometric, surgical, and genetic findings in 15 ears of patients with osteogenesis imperfecta. | Swinnen FK | The Laryngoscope | 2009 | PMID: 19358256 |
Osteogenesis imperfecta: clinical, biochemical and molecular findings. | Venturi G | Clinical genetics | 2006 | PMID: 16879195 |
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 rs72667023 ...
HelpRecord 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.