Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001927083 | SCV002202919 | uncertain significance | Koolen-de Vries syndrome | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 649 of the KANSL1 protein (p.His649Asp). This variant is present in population databases (rs759914921, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with KANSL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1426028). 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 KANSL1 protein function. 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. |
| Fulgent Genetics, |
RCV001927083 | SCV002776189 | uncertain significance | Koolen-de Vries syndrome | 2021-12-22 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002561365 | SCV003676556 | likely benign | Inborn genetic diseases | 2021-12-03 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |