Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003007776 | SCV003303005 | uncertain significance | not provided | 2022-07-02 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1270 of the FAT4 protein (p.Ile1270Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FAT4-related conditions. 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. |
Clinical Genomics Laboratory, |
RCV003458251 | SCV004177166 | uncertain significance | Hennekam lymphangiectasia-lymphedema syndrome 2 | 2023-08-09 | criteria provided, single submitter | clinical testing | The FAT4 c.3808A>C (p.Ile1270Leu) variant, to our knowledge, has not been reported in the medical literature. This variant has been classified in the ClinVar database as a uncertain significance (ClinVar ID 2087017) by a single submitter. FAT4 c.3808A>C (p.Ile1270Leu) is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors suggest that the 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), this variant is classified as being uncertain significance at this time. |