ClinVar Miner

Submissions for variant NM_001127671.2(LIFR):c.254del (p.Asn85fs)

dbSNP: rs886041545
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000295087 SCV000330219 pathogenic not provided 2021-09-08 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 30919572)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002222464 SCV002500692 likely pathogenic Stüve-Wiedemann syndrome 1 2022-03-28 criteria provided, single submitter clinical testing Variant summary: LIFR c.254delA (p.Asn85ThrfsX26) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been cited as pathogenic and as disease-associated in ClinVar and HGMD. The variant was absent in 195382 control chromosomes (gnomAD). c.254delA has been reported in the literature in an individual affected with skeletal dysplasia, bowed lower limbs, camptodactyly, pulmonary hypoplasia, and dysmorphic features; however, authors did not specify the presence of a second pathogenic variant (Al-Dewik_L2019). This report does not provide unequivocal conclusions about association of the variant with Stuve-Wiedemann Syndrome 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV002222464 SCV004810254 pathogenic Stüve-Wiedemann syndrome 1 2024-04-04 criteria provided, single submitter clinical testing

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