Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001924307 | SCV002205918 | uncertain significance | not provided | 2022-07-26 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 3103 of the FAT4 protein (p.Ser3103Arg). This variant is present in population databases (no rsID available, gnomAD no frequency). 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: 1425151). 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. 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, |
RCV005023467 | SCV005657505 | uncertain significance | Van Maldergem syndrome 2; Hennekam lymphangiectasia-lymphedema syndrome 2 | 2024-04-10 | criteria provided, single submitter | clinical testing | |
| Clinical Genomics Laboratory, |
RCV005051936 | SCV005685371 | uncertain significance | Hennekam lymphangiectasia-lymphedema syndrome 2 | 2024-07-02 | criteria provided, single submitter | clinical testing | A FAT4 c.9315C>G (p.Ser3105Arg) variant was identified at a near heterozygous allelic fraction of 49.3%, a frequency which may be consistent with germline origin. This variant, to our knowledge, has not been reported in the medical literature and is only observed on 4/1,613,982 alleles in the general population (gnomAD v4.1.0), indicating that it is not a common variant. The variant has been reported in the ClinVar database as a variant of uncertain clinical significance by one submitter (ClinVar Variation ID: 1425151). Computational predictors suggest that this variant does not impact FAT4 function. 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.9315C>G (p.Ser3105Arg) variant is uncertain at this time. |