NM_000090.4(COL3A1):c.944G>T (p.Gly315Val) AND Ehlers-Danlos syndrome, type 4

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 10, 2016
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:: RCV000470199.9

Allele description [Variation Report for NM_000090.4(COL3A1):c.944G>T (p.Gly315Val)]

NM_000090.4(COL3A1):c.944G>T (p.Gly315Val)

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.944G>T (p.Gly315Val)

HGVS:

NC_000002.12:g.188991715G>T
NG_007404.1:g.22343G>T
NM_000090.4:c.944G>TMANE SELECT
NP_000081.1:p.Gly315Val
NP_000081.2:p.Gly315Val
LRG_3t1:c.944G>T
LRG_3:g.22343G>T
LRG_3p1:p.Gly315Val
NC_000002.11:g.189856441G>T
NM_000090.3:c.944G>T

Protein change:

G315V

Links:

dbSNP: rs587779487

NCBI 1000 Genomes Browser:

rs587779487

Molecular consequence:

NM_000090.4:c.944G>T - 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
SCV000541803	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 10, 2016)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 7695699, 19344236, 24922459, 25758994, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000541803

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 10, 2016)

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	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

Collagen structure and stability.

Shoulders MD, Raines RT.

Annu Rev Biochem. 2009;78:929-58. doi: 10.1146/annurev.biochem.77.032207.120833. Review.

PubMed [citation]

PMID:: 19344236
PMCID:: PMC2846778

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000541803.6

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

Description

In summary, this variant is a novel missense change that affects one of the glycine residues within the triple helix of the COL3A1 protein. For these reasons, it has been classified as Likely Pathogenic. Glycine residues within the triple helix region are important for fibrillar collagens structure and stability (PMID: 7695699, 19344236). In the case of COL3A1 the majority of the missense substitutions at the triple helix domain affect glycine residues (PMID: 24922459, 25758994). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a COL3A1-related disease. This sequence change replaces glycine with valine at codon 315 of the COL3A1 protein (p.Gly315Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine.

#	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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