NM_000090.4(COL3A1):c.2690G>A (p.Gly897Asp) AND Ehlers-Danlos syndrome, type 4

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 6, 2020
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:: RCV001050451.9

Allele description [Variation Report for NM_000090.4(COL3A1):c.2690G>A (p.Gly897Asp)]

NM_000090.4(COL3A1):c.2690G>A (p.Gly897Asp)

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.2690G>A (p.Gly897Asp)

HGVS:

NC_000002.12:g.189004010G>A
NG_007404.1:g.34638G>A
NM_000090.4:c.2690G>AMANE SELECT
NP_000081.2:p.Gly897Asp
LRG_3t1:c.2690G>A
LRG_3:g.34638G>A
NC_000002.11:g.189868736G>A
NM_000090.3:c.2690G>A

Protein change:

G897D

Links:

dbSNP: rs1688529460

NCBI 1000 Genomes Browser:

rs1688529460

Molecular consequence:

NM_000090.4:c.2690G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001214559	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 6, 2020)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 7695699, 8218237, 19344236, 24922459, 25758994, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001214559

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 6, 2020)

germline

clinical testing

PubMed (6)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution.

Bella J, Eaton M, Brodsky B, Berman HM.

Science. 1994 Oct 7;266(5182):75-81.

PubMed [citation]

PMID:: 7695699

Characterization of collagen-like peptides containing interruptions in the repeating Gly-X-Y sequence.

Long CG, Braswell E, Zhu D, Apigo J, Baum J, Brodsky B.

Biochemistry. 1993 Nov 2;32(43):11688-95.

PubMed [citation]

PMID:: 8218237

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001214559.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

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. 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). This variant has been observed in an individual affected with¬†Ehlers‚ÄìDanlos syndrome¬†(PMID:¬†25758994). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 897 of the COL3A1 protein (p.Gly897Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid.

#	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: Sep 29, 2024

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