NM_000090.4(COL3A1):c.1249G>C (p.Gly417Arg) AND Ehlers-Danlos syndrome, type 4

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 24, 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:: RCV001209569.7

Allele description [Variation Report for NM_000090.4(COL3A1):c.1249G>C (p.Gly417Arg)]

NM_000090.4(COL3A1):c.1249G>C (p.Gly417Arg)

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.1249G>C (p.Gly417Arg)

HGVS:

NC_000002.12:g.188994288G>C
NG_007404.1:g.24916G>C
NM_000090.4:c.1249G>CMANE SELECT
NP_000081.2:p.Gly417Arg
LRG_3t1:c.1249G>C
LRG_3:g.24916G>C
NC_000002.11:g.189859014G>C
NM_000090.3:c.1249G>C

Protein change:

G417R

Links:

dbSNP: rs587779637

NCBI 1000 Genomes Browser:

rs587779637

Molecular consequence:

NM_000090.4:c.1249G>C - 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
SCV001381010	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 24, 2019)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 7695699, 8218237, 19344236, 24922459, 25758994, 10706896, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001381010

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 24, 2019)

germline

clinical testing

PubMed (7)
[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 (7)

Details of each submission

From Invitae, SCV001381010.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

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 with clinical features of Ehlers-Danlos syndrome, vascular type (PMID: 10706896). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 417 of the COL3A1 protein (p.Gly417Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine.

#	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: Jun 2, 2024

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