Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001265715 | SCV001443884 | likely pathogenic | Inborn genetic diseases | 2017-12-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001880095 | SCV002170823 | uncertain significance | Familial aplasia of the vermis | 2021-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 563 of the INPP5E protein (p.Arg563Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs371960390, ExAC 0.03%). This variant has been observed in individual(s) with retinitis pigmentosa (Invitae). ClinVar contains an entry for this variant (Variation ID: 985025). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt INPP5E protein function. This variant disrupts the p.Arg563 amino acid residue in INPP5E. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19668216). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |