Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000441534 | SCV000523424 | likely benign | not specified | 2016-02-10 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Baylor Genetics | RCV001329187 | SCV001520551 | uncertain significance | Syndromic X-linked intellectual disability Claes-Jensen type | 2020-01-10 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Labcorp Genetics |
RCV003588631 | SCV004334497 | uncertain significance | Spastic paraplegia | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1445 of the KDM5C protein (p.Arg1445His). This variant is present in population databases (rs782272528, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with KDM5C-related conditions. ClinVar contains an entry for this variant (Variation ID: 383134). 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 KDM5C 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. |