ClinVar Miner

Submissions for variant NM_001127671.2(LIFR):c.2074C>T (p.Arg692Ter)

gnomAD frequency: 0.00002  dbSNP: rs199775294
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized 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

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