Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001095789 | SCV001251638 | uncertain significance | Syndromic X-linked intellectual disability Claes-Jensen type | 2020-01-21 | criteria provided, single submitter | clinical testing | The KDM5C c.1354G>A (p.Gly452Ser) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the Genome Aggregation Database in a region of good sequence coverage, so the variant is presumed to be rare. Based on the limited evidence, the p.Gly452Ser variant is classified as a variant of unknown significance for KDM5C-X-linked intellectual disability. |
| Invitae | RCV001856295 | SCV002309335 | uncertain significance | Spastic paraplegia | 2021-02-23 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 452 of the KDM5C protein (p.Gly452Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant has not been reported in the literature in individuals with KDM5C-related conditions. ClinVar contains an entry for this variant (Variation ID: 873536). 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 expected to disrupt KDM5C protein function. |