Submissions for variant NM_000090.4(COL3A1):c.713G>A (p.Arg238Gln)

gnomAD frequency: 0.00001  dbSNP: rs760324242

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000773424	SCV000907118	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2019-05-05	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 238 of the COL3A1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/250842 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.
GeneDx	RCV001766605	SCV001999088	uncertain significance	not provided	2024-05-29	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Occurs in the triple helical domain at the X position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the X position is not a common mechanism of disease (HGMD)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001869096	SCV002197339	uncertain significance	Ehlers-Danlos syndrome, type 4	2022-08-21	criteria provided, single submitter	clinical testing	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. 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. ClinVar contains an entry for this variant (Variation ID: 628761). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. This variant is present in population databases (rs760324242, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 238 of the COL3A1 protein (p.Arg238Gln).
All of Us Research Program, National Institutes of Health	RCV001869096	SCV004831289	uncertain significance	Ehlers-Danlos syndrome, type 4	2023-06-15	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 238 of the COL3A1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/250842 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.