ClinVar Miner

Submissions for variant NM_014646.2(LPIN2):c.1510C>T (p.Leu504Phe) (rs104895500)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000221897 SCV000279008 uncertain significance not specified 2017-03-27 criteria provided, single submitter clinical testing The L504F variant in the LPIN2 gene has been reported in an individual with psoriasis (personal communication with an external expert, 2008), but, to our knowledge, has not been reported in an individual diagnosed with Majeed syndrome. The L504F variant is observed in 225/66638 (0.34%) alleles from individuals of non-Finnish European background in the ExAC dataset, and no individuals were reported to be homozygous (Lek et al., 2016). However, this variant has been detected in the homozygous state in two presumably healthy individuals tested at GeneDx. The L504F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Leucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret L504F as a variant of uncertain significance.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000221897 SCV000539546 uncertain significance not specified 2016-03-29 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Gene has limited evidence for disease association. Variant is in disease database based on personal communication. Frequency 0.33%
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000084067 SCV000604117 uncertain significance Majeed syndrome 2019-02-15 criteria provided, single submitter clinical testing The LPIN2 c.1510C>T;p.Leu504Phe variant (rs104895500) has not been published in the medical literature, but has been listed in a gene-specific database in an individual with psoriasis (see link below). The variant is listed in the ClinVar database (Variation ID: 97814) and in the general population with an overall allele frequency of 0.3% (724/282640 alleles including 3 homozygotes) in the Genome Aggregation Database. The leucine at codon 504 is moderately conserved across species and computational algorithms (PolyPhen2, SIFT) predict this variant is deleteriou. Due to limited information, the clinical significance of this variant is uncertain. References: Link to LPIN2 in Infevers database:
Invitae RCV000084067 SCV000645163 likely benign Majeed syndrome 2019-12-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000762223 SCV000892502 uncertain significance not provided 2018-12-01 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000084067 SCV000898799 uncertain significance Majeed syndrome 2019-05-07 criteria provided, single submitter clinical testing LPIN2 NM_014646.2 exon 10 p.Leu504Phe (c.1510C>T): This variant has not been reported in the literature but has been reported in 1 individual with psoriasis in the Infevers database ( This variant is present in 0.3% (470/129044) of European alleles in the Genome Aggregation Database ( This variant is present in ClinVar (Variation ID:97814). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Illumina Clinical Services Laboratory,Illumina RCV000084067 SCV001287780 likely benign Majeed syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000084067 SCV000116190 not provided Majeed syndrome no assertion provided not provided

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