Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001970420 | SCV002257055 | uncertain significance | not provided | 2022-03-19 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 3710 of the FAT4 protein (p.Asp3710Tyr). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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, |
RCV003458238 | SCV004177060 | uncertain significance | Hennekam lymphangiectasia-lymphedema syndrome 2 | 2023-09-28 | criteria provided, single submitter | clinical testing | The FAT4 c.11134G>T (p.Asp3712Tyr) variant, to our knowledge, has not been reported in the medical literature. This variant has been classified in the ClinVar database as a variant of uncertain significance (ClinVar ID: 1467504) by a single submitter. FAT4 c.11134G>T (p.Asp3712Tyr) is only observed on 1/152174 alleles in the general population (gnomAD v.3.1.2), indicating it is not a common variant. Computational predictors are uncertain as to the impact of this variant on 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. |