ClinVar Miner

Submissions for variant NM_002296.4(LBR):c.1366C>G (p.Leu456Val)

gnomAD frequency: 0.00001  dbSNP: rs377110126
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489302 SCV000577338 likely pathogenic not provided 2020-12-17 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32827848)
Fulgent Genetics, Fulgent Genetics RCV000763831 SCV000894753 uncertain significance Pelger-Huët anomaly; Greenberg dysplasia; Reynolds syndrome; Regressive spondylometaphyseal dysplasia 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000489302 SCV002313902 uncertain significance not provided 2024-02-24 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 456 of the LBR protein (p.Leu456Val). This variant is present in population databases (rs377110126, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal recessive LBR-related conditions (PMID: 32827848). ClinVar contains an entry for this variant (Variation ID: 426800). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LBR protein function with a positive predictive value of 80%. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002279263 SCV002566868 uncertain significance Connective tissue disorder 2019-04-01 criteria provided, single submitter clinical testing
OMIM RCV001824057 SCV002073664 pathogenic RHIZOMELIC SKELETAL DYSPLASIA WITHOUT PELGER-HUET ANOMALY 2022-03-17 no assertion criteria provided literature only

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.