Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001234981 | SCV001407644 | uncertain significance | Cornelia de Lange syndrome 4 | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 571 of the RAD21 protein (p.Leu571Phe). This variant is present in population databases (rs139935751, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RAD21-related conditions. ClinVar contains an entry for this variant (Variation ID: 961308). 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 RAD21 protein function with a negative 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. |