Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000604634 | SCV000713482 | likely pathogenic | Stuve-Wiedemann syndrome | 2017-09-26 | criteria provided, single submitter | clinical testing | The p.Lys526AsnfsX4 (NM_002310.5 c.1578delA) variant in LIFR has not been previo usly reported in individuals with Stuve-Wiedemann syndrome and was absent from l arge population studies. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 526 and leads to a premature termination codon 4 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Biallelic loss of function o f the LIFR gene has been associated with Stuve-Wiedemann syndrome. In summary, a lthough additional studies are required to fully establish its clinical signific ance, the p.Lys526AsnfsX4 variant is likely pathogenic for Stuve-Wiedemann syndr ome in an autosomal recessive manner based on a predicted null effect. |
| Invitae | RCV003736839 | SCV004551585 | pathogenic | not provided | 2023-05-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 506000). This variant has not been reported in the literature in individuals affected with LIFR-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys526Asnfs*4) 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). |