Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001202114 | SCV001373215 | uncertain significance | Familial aplasia of the vermis | 2022-10-24 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 933822). 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. 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 not expected to disrupt INPP5E protein function. This variant has not been reported in the literature in individuals affected with INPP5E-related conditions. This variant is present in population databases (rs566641584, gnomAD 0.02%). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 101 of the INPP5E protein (p.Glu101Gln). |
| Prevention |
RCV003396820 | SCV004104341 | uncertain significance | INPP5E-related condition | 2022-12-09 | criteria provided, single submitter | clinical testing | The INPP5E c.301G>C variant is predicted to result in the amino acid substitution p.Glu101Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-139333571-C-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |