ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.2752G>A (p.Gly918Arg) (rs1085307896)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489950 SCV000577618 likely pathogenic not provided 2016-03-16 criteria provided, single submitter clinical testing The G918R variant has not been reported as a pathogenic variant or as a benign variant to our knowledge. The G918R was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant results in 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. This substitution occurs at a position that is conserved across species, and in silico analysis predicts G918R is damaging to the protein structure/function. Furthermore, a missense variant affecting the same residue (G918E) and in nearby residues (G912A, G912D, G924C, G924S) have been reported in HGMD in association with EDS type IV (Stenson et al., 2014; Pepin M et al., 2000). Finally, the G918R variant affects a Glycine residue in a Gly-X-Y motif in the triple helical region of the COL3A1 gene, where the majority of missense pathogenic variants occur (Stenson et al., 2014; Symoens et al., 2012).Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659422 SCV000781236 likely pathogenic Ehlers-Danlos syndrome, type 4 2016-11-01 criteria provided, single submitter clinical testing

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