Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000484893 | SCV000565314 | likely pathogenic | not provided | 2015-12-03 | criteria provided, single submitter | clinical testing | The R121W variant in the NDP gene has been reported previously in association with X-linked familial exudative vitreoretinopathy (Meindl et al., 1995; Pelcastre et al., 2010; Fuchs et al., 1995; Wu et al., 2007). The R121W variant was not observed in approximately 6,488 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R121W variant 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. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information R121W is interpreted to be a likely pathogenic variant. |
| Invitae | RCV000484893 | SCV002232781 | pathogenic | not provided | 2021-06-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects NDP protein function (PMID: 26158506). This variant has been observed in individual(s) with exudative vitreoretinopathy (PMID: 7795608, 17296899, 20491809, 8832723, 7558002). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 10688). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 121 of the NDP protein (p.Arg121Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. |
| Human Genetics Bochum, |
RCV003334376 | SCV004042754 | likely pathogenic | Atrophia bulborum hereditaria | 2023-07-12 | criteria provided, single submitter | clinical testing | ACMG criteria used to clasify this variant: PS4_MOD, PP3_MOD, PM2_SUP, PP1 |
| OMIM | RCV000011434 | SCV000031666 | pathogenic | Exudative vitreoretinopathy 2, X-linked | 1997-01-01 | no assertion criteria provided | literature only |