ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.501G>C (p.Glu167Asp) (rs104895079)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282852 SCV000604193 pathogenic none provided 2020-08-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000002652 SCV000696074 likely pathogenic Familial Mediterranean fever 2019-09-19 criteria provided, single submitter clinical testing Variant summary: MEFV c.501G>C (p.Glu167Asp) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 182315 control chromosomes (gnomAD, exomes dataset). c.501G>C (p.E167D) is often observed in the same chromosome (in cis) with a pathogenic variant (c.1437C>G (p.Phe479Leu)) forming a complex allele p.[E167D;F479L] which is also a known pathogenic variant. Nevertheless, E167D has also been reported in the literature in isolation, in homozygous or compound heterozygous state, in a few individuals affected with Familial Mediterranean Fever (e.g. Ceylan_2012, Papa_2017, Ustek_2008). These data indicate that the variant is likely to be associated with disease. In 2012, an international consortium of experts reached a consensus (as part of an agreed set of best practice guidelines) to test for 14 MEFV variants, nine of which were considered pathogenic (including E167D) and 5 of unknown significance (Shinar_2012). In addition, in 2018 the experts international study group for systemic autoinflammatory diseases (INSAID) agreed in a consensus classification of (provisional) likely pathogenic for the variant (Van Gijn_2018). A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Mendelics RCV000002652 SCV001139887 uncertain significance Familial Mediterranean fever 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000588525 SCV001245677 pathogenic not provided 2019-07-01 criteria provided, single submitter clinical testing
Invitae RCV000002652 SCV001416539 uncertain significance Familial Mediterranean fever 2019-08-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 167 of the MEFV protein (p.Glu167Asp). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs104895079, ExAC 0.008%). This variant has been observed frequently in cis (on the same chromosome) with the MEFV p.Phe479Leu variant in individuals with MEFV-related disorders with variable phenotypes and a wide range of severity (including asymptomatic individuals) (PMID: 9668175, 11175300, 12180071, 25708585, 25393764, 21413889, 26351556, 24469716, 29178647). In some of these individuals, an additional MEFV variant was not identified on the opposite allele, while in others, multiple additional MEFV variants were identified. Segregation studies have not been reported for this variant. ClinVar contains an entry for this variant (Variation ID: 2543). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant has been reported in many affected individuals as well as in unaffected individuals. However, 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.
Institute of Human Genetics, University of Leipzig Medical Center RCV001262294 SCV001440108 uncertain significance Familial mediterranean fever, autosomal dominant 2019-01-01 criteria provided, single submitter clinical testing
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV000588525 SCV001449672 likely pathogenic not provided 2017-01-11 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV000002652 SCV001653393 likely pathogenic Familial Mediterranean fever 2021-05-18 criteria provided, single submitter clinical testing
OMIM RCV000002652 SCV000022810 pathogenic Familial Mediterranean fever 2009-11-01 no assertion criteria provided literature only
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000002652 SCV000115875 not provided Familial Mediterranean fever 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.