Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
RCV002262558 | SCV002543553 | uncertain significance | Autoinflammatory syndrome | 2021-11-02 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
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 | |
Gene |
RCV000005190 | SCV000041266 | not provided | Majeed syndrome | no assertion provided | literature only | ||
Unité médicale des maladies autoinflammatoires, |
RCV000005190 | SCV000116191 | not provided | Majeed syndrome | no assertion provided | not provided |