Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001307225 | SCV001496629 | uncertain significance | not provided | 2022-08-01 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1390 of the FAT4 protein (p.Ile1390Thr). This variant is present in population databases (rs201934636, gnomAD 0.04%). 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: 1009702). 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 FAT4 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. |
Gene |
RCV001307225 | SCV001778191 | uncertain significance | not provided | 2020-09-30 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Seattle Children's Hospital Molecular Genetics Laboratory, |
RCV001307225 | SCV002525601 | uncertain significance | not provided | 2020-05-26 | criteria provided, single submitter | clinical testing | The p.Ile1390Thr (c.4169T>C, rs201934636) variant in exon 2 of FAT4 substitutes the isoleucine at position 1390 with threonine. This variant has not been reported as a pathogenic change in the medical literature or patient databases (Human Gene Mutation Database nor ClinGen). This variant is present in large population cohorts at a very low frequency (57 of 280,666 alleles; Genome Aggregation Database v2.1; GRCh37 chr4:126241735). This is a semi-conserved residue and some in silico tools predict this change is damaging (DANN, EIGEN, FATHMM-MKL, M-CAP, MutationAssessor, MutationTaster, PrimateAI and SIFT), while others predict this change is tolerated (DEOGEN2, MVP and REVEL). |