Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000414176 | SCV000492263 | uncertain significance | not specified | 2016-11-27 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the FAT4 gene. The E1110K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E1110K variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E1110K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals; however, Lysine is observed at this position in evolution. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV002521433 | SCV003492066 | uncertain significance | not provided | 2024-11-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1110 of the FAT4 protein (p.Glu1110Lys). This variant is present in population databases (rs377275274, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with FAT4-related conditions. ClinVar contains an entry for this variant (Variation ID: 373650). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt FAT4 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. |
| Fulgent Genetics, |
RCV005033947 | SCV005657883 | uncertain significance | Van Maldergem syndrome 2; Hennekam lymphangiectasia-lymphedema syndrome 2 | 2024-04-04 | criteria provided, single submitter | clinical testing |