ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.1267G>A (p.Gly423Ser) (rs587779631)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Collagen Diagnostic Laboratory,University of Washington RCV000087599 SCV000120489 pathogenic Ehlers-Danlos syndrome, type 4 no assertion criteria provided clinical testing
GeneDx RCV000520450 SCV000617609 likely pathogenic not provided 2018-12-12 criteria provided, single submitter clinical testing The G423S likely pathogenic variant in the COL3A1 gene has been reported in one patient referred for genetic testing for vascular Ehlers-Danlos syndrome (vEDS) (Pepin et al., 2014). However, additional clinical details were not provided. This variant is not observed in large population cohorts (Lek et al., 2016). G423S is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. The G423S 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). Finally, a different likely pathogenic missense variant affecting the same residue (G423D) has also been reported in association with vEDS (Pepin et al., 2014).Therefore, this variant is likely pathogenic.

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