Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003118413 | SCV003788388 | uncertain significance | not provided | 2022-08-06 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with FAT4-related conditions. 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) performed at Invitae indicates that this missense variant is not expected to disrupt FAT4 protein function. This variant is present in population databases (rs767617118, gnomAD 0.007%). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 3493 of the FAT4 protein (p.Ser3493Gly). |
Clinical Genomics Laboratory, |
RCV004560089 | SCV005047076 | uncertain significance | Hennekam lymphangiectasia-lymphedema syndrome 2 | 2024-03-29 | criteria provided, single submitter | clinical testing | The FAT4 c.10483A>G (p.Ser3495Gly) variant was identified at a near heterozygous allele fraction of 49%, a frequency which may be consistent with it being of germline origin. This variant, to our knowledge, has not been reported in the medical literature. Computational predictors suggest that this variant does not impact FAT4 function. The FAT4 c.10483A>G (p.Ser3495Gly) variant has been reported in the ClinVar database as a variant of uncertain significance by one submitter (ClinVar ID: 2419888). This variant is only observed on 10/1,614,002 alleles in the general population (gnomAD v4.0.0), indicating it is not a common variant. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of the FAT4 c.10483A>G (p.Ser3495Gly) variant is uncertain at this time. |