Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000825521 | SCV000966836 | likely pathogenic | Van Maldergem syndrome | 2017-01-30 | criteria provided, single submitter | clinical testing | The p.Arg2234* (NM_024582.4 c.6700C>T) variant in FAT4 has not been reported in the literature and was absent from large population studies. This nonsense varia nt leads to a premature termination codon at position 2234, which is predicted t o lead to a truncated or absent protein. Biallelic loss of function of the FAT4 gene has been associated with two syndromes that have overlapping features: Van Maldergem syndrome 2 / Hennekam lymphangiectasia-lymphedema syndrome 2. In summa ry, although additional studies are required to fully establish a null effect on the protein, the p.Arg2234* variant in FAT4 is likely pathogenic for Van Malder gem syndrome 2 / Hennekam lymphangiectasia-lymphedema syndrome 2 spectrum disord ers in an autosomal recessive manner based upon its predicted functional impact. |
| Invitae | RCV003736915 | SCV004551579 | pathogenic | not provided | 2023-06-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 666967). This variant has not been reported in the literature in individuals affected with FAT4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg2234*) in the FAT4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FAT4 are known to be pathogenic (PMID: 24056717, 24913602). |