ClinVar Genomic variation as it relates to human health
NM_000090.4(COL3A1):c.611G>A (p.Gly204Asp)
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_000090.4(COL3A1):c.611G>A (p.Gly204Asp)
Variation ID: 101351 Accession: VCV000101351.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q32.2 2: 188988618 (GRCh38) [ NCBI UCSC ] 2: 189853344 (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 13, 2014 Feb 14, 2024 Dec 3, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000090.4:c.611G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000081.2:p.Gly204Asp missense NC_000002.12:g.188988618G>A NC_000002.11:g.189853344G>A NG_007404.1:g.19246G>A LRG_3:g.19246G>A LRG_3t1:c.611G>A LRG_3p1:p.Gly204Asp P02461:p.Gly204Asp NP_000081.1:p.Gly204Asp - Protein change
- Other names
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- Canonical SPDI
- NC_000002.12:188988617: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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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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COL3A1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
2994 | 3119 |
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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Likely pathogenic (2) |
criteria provided, single submitter
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Dec 3, 2021 | RCV000087589.12 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 11, 2016 | RCV002313844.8 |
Submissions - Germline
Classification
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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
(Oct 11, 2016)
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criteria provided, single submitter
Method: clinical testing
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Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000738536.4
First in ClinVar: Apr 14, 2018 Last updated: Nov 29, 2022 |
Comment:
The p.G204D pathogenic mutation (also known as c.611G>A), located in coding exon 7 of the COL3A1 gene, results from a G to A substitution at … (more)
The p.G204D pathogenic mutation (also known as c.611G>A), located in coding exon 7 of the COL3A1 gene, results from a G to A substitution at nucleotide position 611. The glycine at codon 204 is replaced by aspartic acid, an amino acid with similar properties. The majority (approximately two-thirds) of COL3A1 mutations identified to date have involved the substitution of another amino acid for glycine within the triple-helical domain (Schwarze U et al. Am J Hum Genet. 1997;61(6):1276-1286; Pepin MG et al. Genet Med. 2014;16(12):881-8). This particular mutation (with legacy nomenclature p.G37D) has been reported in individuals from Ehlers-Danlos syndrome type IV (vascular type) cohorts, and cultured skin fibroblasts from one of the patients were shown to secrete reduced levels of type III collagen (Giunta C et al. Hum. Mutat. 2000;16:176-7; Pepin MG et al. Genet. Med. 2014;16:881-8). Internal structural analysis indicates this alteration to be structurally deleterious, and a likely disease-causing variant, p.G204S, has been described in the same codon (Pepin M et al. N. Engl. J. Med. 2000;342:673-80). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Likely pathogenic
(Dec 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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Ehlers-Danlos syndrome, type 4
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002279308.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This variant is also known as c.713G>A (p.G37D). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed … (more)
This variant is also known as c.713G>A (p.G37D). 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. This variant disrupts the triple helix domain of COL3A1. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL3A1, variants that affect these glycine residues are significantly enriched in individuals with disease (PMID: 24922459, 25758994) compared to the general population (ExAC). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL3A1 protein function. ClinVar contains an entry for this variant (Variation ID: 101351). This missense change has been observed in individual(s) with Ehlers-Danlos syndrome (PMID: 10923041). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 204 of the COL3A1 protein (p.Gly204Asp). (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Ehlers-Danlos syndrome, type 4
Affected status: yes
Allele origin:
germline
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Collagen Diagnostic Laboratory, University of Washington
Accession: SCV000120479.1
First in ClinVar: Mar 13, 2014 Last updated: Mar 13, 2014 |
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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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The type of variants at the COL3A1 gene associates with the phenotype and severity of vascular Ehlers-Danlos syndrome. | Frank M | European journal of human genetics : EJHG | 2015 | PMID: 25758994 |
Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV). | Pepin MG | Genetics in medicine : official journal of the American College of Medical Genetics | 2014 | PMID: 24922459 |
Collagen structure and stability. | Shoulders MD | Annual review of biochemistry | 2009 | PMID: 19344236 |
Characterization of 11 new mutations in COL3A1 of individuals with Ehlers-Danlos syndrome type IV: preliminary comparison of RNase cleavage, EMC and DHPLC assays. | Giunta C | Human mutation | 2000 | PMID: 10923041 |
Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution. | Bella J | Science (New York, N.Y.) | 1994 | PMID: 7695699 |
Characterization of collagen-like peptides containing interruptions in the repeating Gly-X-Y sequence. | Long CG | Biochemistry | 1993 | PMID: 8218237 |
Text-mined citations for rs587779626 ...
HelpRecord last updated Apr 20, 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.