ClinVar Miner

Submissions for variant NM_001375808.2(LPIN2):c.2201C>T (p.Ser734Leu)

gnomAD frequency: 0.00001  dbSNP: rs80338807
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000222509 SCV000279014 pathogenic not provided 2013-02-19 criteria provided, single submitter clinical testing The S734L missense mutation in the LPIN2 gene has been reported previously in association with Majeed syndrome (Ferguson et al., 2005). This mutation occurs at a conserved position in the LPIN2 protein that is part of the C-LIP domain region. Functional studies of this mutation revealed that its presence abolishes the normal phosphatidate phosphatase (PAP) enzymatic activity of the LPIN2 protein (Donkor et al., 2009).
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002262558 SCV002543553 uncertain significance Autoinflammatory syndrome 2021-11-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000005190 SCV002548494 pathogenic Majeed syndrome 2022-05-05 criteria provided, single submitter clinical testing Variant summary: LPIN2 c.2201C>T (p.Ser734Leu) results in a non-conservative amino acid change located in the LNS2/PITP domain (IPR031315) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251130 control chromosomes (gnomAD). c.2201C>T has been reported in the literature in multiple homozygous individuals affected with Majeed Syndrome (Ferguson_2005, Moussa_2017). These data indicate that the variant is very likely to be associated with disease. A publication also reported experimental evidence evaluating an impact on protein function, and demonstrated that the serine to leucine substitution at the analogous serine residue (Ser 731) in a mouse model completely abolished phosphatidate phosphatase (PAP) activity of the variant protein (Donkor_2009). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000005190 SCV000025367 pathogenic Majeed syndrome 2005-07-01 no assertion criteria provided literature only
GeneReviews RCV000005190 SCV000041266 not provided Majeed syndrome no assertion provided literature only
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000005190 SCV000116191 not provided Majeed syndrome no assertion provided not provided

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.