Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001926623 | SCV002207088 | uncertain significance | not provided | 2021-05-26 | criteria provided, single submitter | clinical testing | 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. 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"). This variant has not been reported in the literature in individuals with FAT4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with asparagine at codon 1936 of the FAT4 protein (p.Asp1936Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. |
Ambry Genetics | RCV004044269 | SCV004869792 | uncertain significance | Inborn genetic diseases | 2024-01-23 | criteria provided, single submitter | clinical testing | The c.5806G>A (p.D1936N) alteration is located in exon 4 (coding exon 4) of the FAT4 gene. This alteration results from a G to A substitution at nucleotide position 5806, causing the aspartic acid (D) at amino acid position 1936 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Clinical Genomics Laboratory, |
RCV005051937 | SCV005685405 | uncertain significance | Hennekam lymphangiectasia-lymphedema syndrome 2 | 2024-06-03 | criteria provided, single submitter | clinical testing | A FAT4 c.5806G>A (p.Asp1936Asn) variant was identified at a near heterozygous allelic fraction, a frequency which may be consistent with germline origin. To our knowledge, this variant has not been reported in the medical literature and is only observed on 10/1,609,746 alleles in the general population (gnomAD v.4.1.0), indicating it is not a common variant. This variant has been reported in the ClinVar database as a germline variant of uncertain significance by two submitters (ClinVar ID: 1425420). 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. |