Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
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, |
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, |
RCV001002011 | SCV001462558 | uncertain significance | Stuve-Wiedemann syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |