Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001888744 | SCV002152919 | uncertain significance | Pitt-Hopkins syndrome | 2023-09-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 413 of the TCF4 protein (p.Gly413Arg). This variant is present in population databases (rs768214584, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TCF4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1385288). 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 TCF4 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. |