Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001046738 | SCV001210652 | uncertain significance | Familial aplasia of the vermis | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 198 of the INPP5E protein (p.Ser198Thr). This variant is present in population databases (rs141286608, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with INPP5E-related conditions. ClinVar contains an entry for this variant (Variation ID: 844001). 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 with a negative predictive value of 95%. 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. |
Ambry Genetics | RCV002552606 | SCV003711309 | uncertain significance | Inborn genetic diseases | 2021-07-27 | criteria provided, single submitter | clinical testing | The c.593G>C (p.S198T) alteration is located in exon 1 (coding exon 1) of the INPP5E gene. This alteration results from a G to C substitution at nucleotide position 593, causing the serine (S) at amino acid position 198 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV003130119 | SCV003813390 | uncertain significance | not provided | 2020-03-02 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003928680 | SCV004740121 | uncertain significance | INPP5E-related condition | 2023-12-11 | criteria provided, single submitter | clinical testing | The INPP5E c.593G>C variant is predicted to result in the amino acid substitution p.Ser198Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0066% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |