ClinVar Miner

Submissions for variant NM_014646.2(LPIN2):c.698C>T (p.Thr233Ile) (rs139654849)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000687638 SCV000815218 uncertain significance Majeed syndrome 2018-07-08 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 233 of the LPIN2 protein (p.Thr233Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs139654849, ExAC 0.04%). This variant has not been reported in the literature in individuals with LPIN2-related disease. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000687638 SCV001160145 uncertain significance Majeed syndrome 2018-12-18 criteria provided, single submitter clinical testing The LPIN2 c.698C>T; p.Thr233Ile variant (rs139654849), to our knowledge, is not reported in the medical literature or in gene-specific databases. The variant is reported in the ClinVar database (Variation ID: 567527) and in the general population with an allele frequency of 0.1% (27/281554 alleles) in the Genome Aggregation Database. The amino acid at this position is weakly conserved and computational algorithms (PolyPhen-2, SIFT) predict this variant is tolerated. Considering available information, the clinical significance of this variant cannot be determined with certainty.

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.