NM_000090.4(COL3A1):c.1869+1G>C AND Ehlers-Danlos syndrome, type 4

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 3, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000087552.9

Allele description [Variation Report for NM_000090.4(COL3A1):c.1869+1G>C]

NM_000090.4(COL3A1):c.1869+1G>C

Gene:

COL3A1:collagen type III alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q32.2

Genomic location:

Preferred name:

NM_000090.4(COL3A1):c.1869+1G>C

HGVS:

NC_000002.12:g.188997390G>C
NG_007404.1:g.28018G>C
NM_000090.4:c.1869+1G>CMANE SELECT
NP_000081.1:p.Gly606_Thr623del
LRG_3t1:c.1869+1G>C
LRG_3:g.28018G>C
NC_000002.11:g.189862116G>C
NM_000090.3:c.1869+1G>C

Links:

dbSNP: rs587779600

NCBI 1000 Genomes Browser:

rs587779600

Molecular consequence:

NM_000090.4:c.1869+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

Observations:

Condition(s)

Name:: Ehlers-Danlos syndrome, type 4
Synonyms:: Ehlers-Danlos syndrome vascular type; Ehlers Danlos syndrome, ecchymotic type; Ehlers Danlos syndrome, arterial type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0017314; MedGen: C0268338; Orphanet: 286; OMIM: 130050

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000120439	Collagen Diagnostic Laboratory, University of Washington	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001375279	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 3, 2019)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 23293852, 20518783, 24922459, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000120439

Collagen Diagnostic Laboratory, University of Washington

no assertion criteria provided

Pathogenic

germline

clinical testing

SCV001375279

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 3, 2019)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Patient with the vascular type of Ehlers-Danlos syndrome, with a novel point-mutation in the COL3A1 gene.

Shimaoka Y, Hayashi S, Hamasaki Y, Terui K, Hatamochi A.

J Dermatol. 2013 Mar;40(3):226-8. doi: 10.1111/1346-8138.12057. Epub 2013 Jan 7. No abstract available.

PubMed [citation]

PMID:: 23293852

See all PubMed Citations (5)

Details of each submission

From Collagen Diagnostic Laboratory, University of Washington, SCV000120439.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001375279.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL3A1 are known to be pathogenic (PMID: 24922459). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 20518783, 23293852). Disruption of this splice site has been observed in individuals with clinical features of vascular Ehlers Danlos syndrome (PMID: 23293852, 20518783, 24922459, Invitae). This variant is also known as g.IVS27+1G>C in the literature. ClinVar contains an entry for this variant (Variation ID: 101314). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 26 of the COL3A1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 25, 2025

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