Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Centre for Mendelian Genomics, |
RCV001196089 | SCV001366544 | uncertain significance | Intellectual disability-severe speech delay-mild dysmorphism syndrome | 2019-05-06 | criteria provided, single submitter | clinical testing | This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3. |
| Ambry Genetics | RCV002348643 | SCV002647254 | likely benign | Inborn genetic diseases | 2019-12-11 | 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. |
| Invitae | RCV002559246 | SCV003508892 | uncertain significance | not provided | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 40 of the FOXP1 protein (p.Glu40Val). This variant is present in population databases (rs765070623, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with FOXP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 930431). 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 FOXP1 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. |
| Centre de Biologie Pathologie Génétique, |
RCV001251757 | SCV001427499 | likely benign | Intellectual disability | 2019-01-01 | no assertion criteria provided | clinical testing |