ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.674G>C (p.Gly225Ala) (rs587779533)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000617475 SCV000738521 uncertain significance Cardiovascular phenotype 2016-03-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
Collagen Diagnostic Laboratory,University of Washington RCV000087708 SCV000120601 pathogenic Ehlers-Danlos syndrome, type 4 no assertion criteria provided clinical testing
GeneDx RCV000489400 SCV000576486 pathogenic not provided 2017-05-03 criteria provided, single submitter clinical testing The G225A pathogenic variant in the COL3A1 gene has previously been reported in one individual with vascular Ehlers Danlos syndrome (EDS type IV) (Pepin et al., 2014). In addition, different missense variants affecting the same residue (G225V, G225D) have also been reported in association with vascular EDS (Pepin et al., 2014; Drera et al., 2011). The G225A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although the G225A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, it occurs at a position that is conserved across species. In addition, in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, the G225A variant affects a Glycine residue in a Gly-X-Y motif in the triple helical region of the COL3A1 gene, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012).

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