Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV001171741 | SCV001334579 | uncertain significance | not provided | 2020-02-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001171741 | SCV002170278 | uncertain significance | not provided | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1515 of the FAT4 protein (p.Val1515Met). This variant is present in population databases (rs773912269, gnomAD 0.01%). 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: 916196). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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, |
RCV003458223 | SCV004176984 | uncertain significance | Hennekam lymphangiectasia-lymphedema syndrome 2 | 2023-09-01 | criteria provided, single submitter | clinical testing | The FAT4 c.4543G>A (p.Val1515Met) variant was identified at a near heterozygous allelic fraction. This variant, to our knowledge, has not been reported in the medical literature. This variant has been reported in the ClinVar database as a variant of uncertain significance by two submitters (ClinVar ID: 916196) and has been reported in one case in the cancer database COSMIC (Genomic Mutation ID : COSV67902393). This variant is only observed on 8/152222 alleles in the general population (gnomAD v.3.1.2), indicating it is not a common variant. Computational predictors are conflicting as to the impact of this variant on the 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. |