ClinVar Miner

Submissions for variant NM_000243.3(MEFV):c.2076_2078del (p.Ile692del) (rs104895093)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000487146 SCV000224796 pathogenic not provided 2014-10-14 criteria provided, single submitter clinical testing
GeneDx RCV000487146 SCV000565123 pathogenic not provided 2016-12-19 criteria provided, single submitter clinical testing The c.2076_2078delAAT variant has been published previously in association with familial Mediterranean fever (Sabbagh et al., 2008; Jarjour et al., 2010; Salehzadeh et al., 2015), and has been observed on opposite alleles (in trans) with pathogenic variants in the MEFV gene at GeneDx.. The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The variant results in the in-frame deletion of an Isoleucine residue within the B30.2/SPRY domain, a domain which is critical for protein function (Masters et al., 2009). Therefore, we consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000487146 SCV001134280 pathogenic not provided 2019-02-20 criteria provided, single submitter clinical testing The best available variant frequency is uninformative. Statistically enriched in patients compared to ethnically matched controls. Found in at least one symptomatic patient. Occurs in multiple cases with a recessive pathogenic variant in the same gene.
Mendelics RCV000083737 SCV001139827 uncertain significance Familial Mediterranean fever 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000942 SCV001158041 likely pathogenic not specified 2018-12-06 criteria provided, single submitter clinical testing The MEFV c.2076_2078delAAT; p.Ile692del variant (rs104895093), is reported in the literature in multiple individuals affected with familial Mediterranean fever (FMF) (Bernot 1998, Salehzadeh 2015). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 97485), and is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant deletes a single isoleucine residue leaving the rest of the protein in-frame. This variant affects a residue in the conserved region of the B30.2 domain, which contains pathogenic MEFV variants associated with the most severe FMF symptoms (Moradian 2017). Based on available information, the p.Ile692del variant is considered to be likely pathogenic. References: Bernot A et al. Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF). Hum Mol Genet. 1998 Aug;7(8):1317-25. Moradian MM et al. Comprehensive analysis of mutations in the MEFV gene reveal that the location and not the substitution type determines symptom severity in FMF. Mol Genet Genomic Med. 2017 Nov;5(6):742-750. Salehzadeh F et al. MEFV Gene Profile in Northwest of Iran, Twelve Common MEFV Gene Mutations Analysis in 216 Patients with Familial Mediterranean Fever. Iran J Med Sci. 2015 Jan;40(1):68-72.
Invitae RCV000083737 SCV001215382 uncertain significance Familial Mediterranean fever 2019-11-26 criteria provided, single submitter clinical testing This variant, c.2076_2078del, results in the deletion of 1 amino acid(s) of the MEFV protein (p.Ile692del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with familial mediterranean fever (PMID: 29047407, 9668175, 21246368, 15018633, 22019805, 29379228, 25648235, 21413889, 28302131, 14578331, 19253030, 17566872). ClinVar contains an entry for this variant (Variation ID: 97485). Experimental studies and prediction algorithms are not available or were not evaluated for this variant, and the functional significance of the affected amino acid(s) is currently unknown. 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.
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV000487146 SCV001449622 pathogenic not provided 2015-09-16 criteria provided, single submitter clinical testing
OMIM RCV000083737 SCV000022813 pathogenic Familial Mediterranean fever 1998-08-01 no assertion criteria provided literature only
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000083737 SCV000115830 not provided Familial Mediterranean fever no assertion provided not provided
GeneReviews RCV000083737 SCV000484967 pathogenic Familial Mediterranean fever 2016-12-15 no assertion criteria provided literature only
Counsyl RCV000083737 SCV001132430 likely pathogenic Familial Mediterranean fever 2019-03-15 no assertion criteria provided clinical testing

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