ClinVar Genomic variation as it relates to human health
NM_001854.4(COL11A1):c.2735C>T (p.Pro912Leu)
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.
Uncertain significance(4); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001854.4(COL11A1):c.2735C>T (p.Pro912Leu)
Variation ID: 876781 Accession: VCV000876781.15
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p21.1 1: 102978727 (GRCh38) [ NCBI UCSC ] 1: 103444283 (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 31, 2020 Feb 14, 2024 Dec 18, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001854.4:c.2735C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001845.3:p.Pro912Leu missense NM_001190709.2:c.2618C>T NP_001177638.1:p.Pro873Leu missense NM_080629.3:c.2771C>T NP_542196.2:p.Pro924Leu missense NM_080630.4:c.2387C>T NP_542197.3:p.Pro796Leu missense NR_134980.2:n.3095C>T non-coding transcript variant NC_000001.11:g.102978727G>A NC_000001.10:g.103444283G>A NG_008033.2:g.134770C>T - Protein change
- P873L, P796L, P912L, P924L
- Other names
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- Canonical SPDI
- NC_000001.11:102978726: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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0.00080 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00009
Trans-Omics for Precision Medicine (TOPMed) 0.00019
Exome Aggregation Consortium (ExAC) 0.00020
The Genome Aggregation Database (gnomAD), exomes 0.00023
1000 Genomes Project 30x 0.00062
1000 Genomes Project 0.00080
- 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 | ||
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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
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. |
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COL11A1 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2595 | 2689 |
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. |
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Likely benign (1) |
criteria provided, single submitter
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Jan 13, 2018 | RCV001101958.4 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Oct 25, 2021 | RCV001101959.5 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Dec 18, 2023 | RCV001664688.13 |
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 benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Stickler syndrome type 2
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001258602.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
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Uncertain significance
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Fibrochondrogenesis 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001258603.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Uncertain significance
(Oct 25, 2021)
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criteria provided, single submitter
Method: clinical testing
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Fibrochondrogenesis 1
Affected status: yes
Allele origin:
unknown
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3billion
Accession: SCV002014715.1
First in ClinVar: Nov 20, 2021 Last updated: Nov 20, 2021 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0002, PM2). it has been reported as uncertain … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0002, PM2). it has been reported as uncertain significance or likley benign (ClinVar ID: VCV000876781.3) Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Barrel-shaped chest (present) , Hypertelorism (present) , Low-set ears (present) , Ptosis (present) , Posteriorly rotated ears (present) , Short chin (present) , Triangular face … (more)
Barrel-shaped chest (present) , Hypertelorism (present) , Low-set ears (present) , Ptosis (present) , Posteriorly rotated ears (present) , Short chin (present) , Triangular face (present) , Clinodactyly (present) , Cryptorchidism (present) , Lymphedema (present) (less)
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Uncertain significance
(Jul 14, 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: SCV001872621.4
First in ClinVar: Sep 19, 2021 Last updated: Jul 22, 2023 |
Comment:
Identified in a patient referred for genetic testing for hearing loss, reported as p.P924L using alternate nomenclature (Miyagawa et al., 2013); however, additional clinical information … (more)
Identified in a patient referred for genetic testing for hearing loss, reported as p.P924L using alternate nomenclature (Miyagawa et al., 2013); however, additional clinical information was not provided; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23967202) (less)
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Uncertain significance
(Jul 26, 2022)
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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: SCV003831144.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Likely benign
(Dec 18, 2023)
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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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Invitae
Accession: SCV002362799.3
First in ClinVar: Apr 08, 2022 Last updated: Feb 14, 2024 |
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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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs192842970 ...
HelpRecord last updated Mar 17, 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.