Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
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, |
RCV000659422 | SCV000781236 | likely pathogenic | Ehlers-Danlos syndrome, type 4 | 2016-11-01 | criteria provided, single submitter | clinical testing |