NM_000090.4(COL3A1):c.2032G>C (p.Gly678Arg) AND Ehlers-Danlos syndrome, type 4

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 26, 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:: RCV004790006.1

Allele description [Variation Report for NM_000090.4(COL3A1):c.2032G>C (p.Gly678Arg)]

NM_000090.4(COL3A1):c.2032G>C (p.Gly678Arg)

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.2032G>C (p.Gly678Arg)

HGVS:

NC_000002.12:g.188999294G>C
NG_007404.1:g.29922G>C
NM_000090.4:c.2032G>CMANE SELECT
NP_000081.1:p.Gly678Arg
NP_000081.2:p.Gly678Arg
LRG_3t1:c.2032G>C
LRG_3:g.29922G>C
LRG_3p1:p.Gly678Arg
NC_000002.11:g.189864020G>C
NM_000090.3:c.2032G>C

Protein change:

G678R

Molecular consequence:

NM_000090.4:c.2032G>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
SCV005399183	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 26, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 2934644, 21637106, 28183226, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005399183

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 26, 2020)

germline

clinical testing

PubMed (4)
[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

Myoglobinuric renal failure in Huntington's chorea.

Jankovic J.

Neurology. 1986 Jan;36(1):138-9. No abstract available.

PubMed [citation]

PMID:: 2934644

COL3A1 haploinsufficiency results in a variety of Ehlers-Danlos syndrome type IV with delayed onset of complications and longer life expectancy.

Leistritz DF, Pepin MG, Schwarze U, Byers PH.

Genet Med. 2011 Aug;13(8):717-22. doi: 10.1097/GIM.0b013e3182180c89.

PubMed [citation]

PMID:: 21637106

See all PubMed Citations (4)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV005399183.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Likely Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene (PMID: 21637106). (N) 0104 - Dominant Negative is a mechanism of disease for this gene (PMID: 2934644). (N) 0108 - This gene is known to be associated with both recessive and dominant disease (OMIM). (N) 0112 – Missense variants in this gene have been reported with variable expressivity and variable age of onset (PMID: 28183226; GeneReviews). (N) 0200 - Variant is predicted to result in a missense amino acid change from glycine to arginine (exon 30). (N) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0501 - Missense variant consistently predicted to be damaging by multiple in-silico tools or highly conserved with a major amino acid change. (P) 0601 - Variant affects at least one well-established (essential) functional domain or motif. This variant affects a glycine residue of the Gly-X-Y repeat within the triple helical region (PDB) (P) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign

#	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: Jan 13, 2025

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