Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002664204 | SCV003523475 | pathogenic | Orofacial cleft 6, susceptibility to; Popliteal pterygium syndrome; Van der Woude syndrome | 2021-12-14 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Glu92 amino acid residue in IRF6. Other variant(s) that disrupt this residue have been observed in individuals with IRF6-related conditions (PMID: 19282774, 21045959), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt IRF6 protein function. This missense change has been observed in individuals with van der Woude syndrome (PMID: 19282774). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 92 of the IRF6 protein (p.Glu92Lys). |