ClinVar Miner

Submissions for variant NM_001127671.2(LIFR):c.406C>G (p.Pro136Ala)

gnomAD frequency: 0.00001  dbSNP: rs761024368
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001002011 SCV001159827 uncertain significance Stuve-Wiedemann syndrome 2018-07-19 criteria provided, single submitter clinical testing The LIFR c.406C>G; p.Pro136Ala variant (rs761024368), to our knowledge, is not described in the medical literature or in gene-specific databases. It is observed in the general population at a low overall frequency of 0.001% (3/245838 alleles) in the Genome Aggregation Database. The proline at codon 136 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. However, due to the lack of clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty.
Fulgent Genetics, Fulgent Genetics RCV002479193 SCV002793691 uncertain significance Stüve-Wiedemann syndrome 1 2021-07-25 criteria provided, single submitter clinical testing
Invitae RCV002549168 SCV003474584 uncertain significance not provided 2022-04-09 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 136 of the LIFR protein (p.Pro136Ala). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with LIFR-related conditions. ClinVar contains an entry for this variant (Variation ID: 811716). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Natera, Inc. RCV001002011 SCV001462558 uncertain significance Stuve-Wiedemann syndrome 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.