ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.877A>G (p.Asn293Asp)

dbSNP: rs1131691328
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493441 SCV000581882 uncertain significance not provided 2017-05-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL3A1 gene. The N293D variant has not been published as pathogenic or been reported as benign to our knowledge. Thid variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The N293D variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, while the N293D variant is located in the triple helical region of the COL3A1 gene, it does not affect a Glycine residue in a Gly-X-Y motif, as the majority of pathogenic missense variants do (Stenson et al., 2014; Symoens et al., 2012).
Labcorp Genetics (formerly Invitae), Labcorp RCV000634708 SCV000756043 uncertain significance Ehlers-Danlos syndrome, type 4 2022-06-03 criteria provided, single submitter clinical testing 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: 429338). This missense change has been observed in individual(s) with clinical features of COL3A1-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 293 of the COL3A1 protein (p.Asn293Asp). 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.

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