Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002585409 | SCV003493170 | uncertain significance | not provided | 2024-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 3690 of the FAT4 protein (p.His3690Tyr). This variant is present in population databases (rs749981245, gnomAD 0.003%). 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: 2177175). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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, |
RCV004560048 | SCV005047136 | uncertain significance | Hennekam lymphangiectasia-lymphedema syndrome 2 | 2024-04-13 | criteria provided, single submitter | clinical testing | The FAT4 c.11074C>T (p.His3692Tyr) variant was identified at a near heterozygous allelic fraction of 49%, a frequency which may be consistent with it being of germline origin. The variant has been reported in the literature in a germline state in a patient with AML (Yang, Fei et al., PMID: 34482403). It is only observed on 14/1,614,042 alleles in the general population (gnomAD v.4.0.0), indicating that it is not a common variant. This variant has been reported in the ClinVar database as a variant of uncertain significance by one submitter (ClinVar ID: 2177175). 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), the clinical significance of this variant is uncertain at this time. |
| Gene |
RCV002585409 | SCV005383014 | uncertain significance | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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 |