Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000169665 | SCV000221195 | likely pathogenic | Stuve-Wiedemann syndrome | 2014-03-19 | criteria provided, single submitter | clinical testing | The Arg692X variant in LIFR gene has not been reported in the literature but has been identified in 1/1319 European chromosomes by the ClinSeq project. This nonsense variant leads to a premature termination codon at position 692, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the LIFR gene is strongly associated with Stuve-Wiedemann syndrome (SWS). In summary, this variant is likely pathogenic, though additional studies are required to fully establish its clinical significance. |
| Invitae | RCV001051726 | SCV001215896 | pathogenic | not provided | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg692*) in the LIFR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LIFR are known to be pathogenic (PMID: 14740318). This variant is present in population databases (rs199775294, gnomAD 0.08%). This premature translational stop signal has been observed in individuals with Stuve-Wiedemann syndrome (PMID: 24988918). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 189235). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000169665 | SCV000222920 | pathogenic | Stuve-Wiedemann syndrome | 2022-02-16 | no assertion criteria provided | literature only |