Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000503808 | SCV000597423 | uncertain significance | not specified | 2015-11-12 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003617819 | SCV004513882 | uncertain significance | Pitt-Hopkins syndrome | 2023-08-04 | criteria provided, single submitter | clinical testing | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TCF4 protein function. ClinVar contains an entry for this variant (Variation ID: 436966). This missense change has been observed in at least one individual who was not affected with TCF4-related conditions (Invitae). This variant has not been reported in the literature in individuals affected with TCF4-related conditions. This variant is present in population databases (rs756279357, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 297 of the TCF4 protein (p.Thr297Met). |