Submissions for variant NM_001375808.2(LPIN2):c.1510C>T (p.Leu504Phe)

gnomAD frequency: 0.00253  dbSNP: rs104895500

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000762223	SCV000279008	likely benign	not provided	2020-04-15	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham 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	2023-09-08	criteria provided, single submitter	clinical testing	The LPIN2 c.1510C>T; p.Leu504Phe variant (rs104895500), has been reported in the literature in two individuals with suspected familial Mediterranean fever, but with alternative molecular explanations for disease (Bozgeyik 2020). The variant has also been reported in an individual with psoriasis (see link below). The variant is listed in the ClinVar database (Variation ID: 97814) and is reported in the general population with an overall allele frequency of 0.3% (724/282,640 alleles, including 3 homozygotes) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.675). Due to limited information, the clinical significance of the p.Leu504Phe variant is uncertain at this time. References: Link to variant in Infevers database: https://infevers.umai-montpellier.fr/web/search.php?n=7 Bozgeyik E et al. Next-generation screening of a panel of genes associated with periodic fever syndromes in patients with Familial Mediterranean Fever and their clinical characteristics. Genomics. 2020;112(4):2755-2762. PMID: 32199921.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000084067	SCV000645163	likely benign	Majeed syndrome	2025-02-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000762223	SCV000892502	likely benign	not provided	2025-01-01	criteria provided, single submitter	clinical testing	LPIN2: BS2
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000084067	SCV000898799	uncertain significance	Majeed syndrome	2021-03-30	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 (https://infevers.umai-montpellier.fr/web/detail_mutation.php). This variant is present in 0.3% (470/129044) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/18-2929103-G-A). 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 Laboratory Services, 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000762223	SCV001712927	uncertain significance	not provided	2021-05-19	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262674	SCV002543256	likely benign	Autoinflammatory syndrome	2022-01-31	criteria provided, single submitter	clinical testing
Unité médicale des maladies autoinflammatoires, CHRU Montpellier	RCV000084067	SCV000116190	not provided	Majeed syndrome		no assertion provided	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000762223	SCV002034933	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000762223	SCV002037852	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003915108	SCV004731761	likely benign	LPIN2-related disorder	2023-09-29	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).