Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000441814 | SCV000528851 | likely benign | not specified | 2016-06-22 | 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. |
New York Genome Center | RCV004799208 | SCV001431193 | uncertain significance | Koolen-de Vries syndrome | 2021-12-22 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV004799208 | SCV005846315 | uncertain significance | Koolen-de Vries syndrome | 2024-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1007 of the KANSL1 protein (p.Arg1007Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurodevelopmental disorders (PMID: 33004838). This missense change has been observed in at least one individual who was not affected with KANSL1-related conditions (internal data). ClinVar contains an entry for this variant (Variation ID: 387002). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt KANSL1 protein function with a positive predictive value of 80%. 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. |