Submissions for variant NM_000090.4(COL3A1):c.821A>G (p.Glu274Gly)

dbSNP: rs1688177791

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002568159	SCV003459363	uncertain significance	Ehlers-Danlos syndrome, type 4	2022-10-21	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 274 of the COL3A1 protein (p.Glu274Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of COL3A1-related conditions (PMID: 29907982). ClinVar contains an entry for this variant (Variation ID: 1174864). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL3A1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health	RCV003528309	SCV004361449	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-06-15	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with glycine at codon 274 of the COL3A1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with thoracic aortic aneurysm and dissection (PMID: 29907982). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health	RCV002568159	SCV004829744	uncertain significance	Ehlers-Danlos syndrome, type 4	2023-08-08	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with glycine at codon 274 of the COL3A1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with thoracic aortic aneurysm and dissection (PMID: 29907982). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529094	SCV001741961	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001529094	SCV001809333	uncertain significance	not provided		no assertion criteria provided	clinical testing