ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.2160C>G (p.Ile720Met) (rs104895102)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000083751 SCV000818062 uncertain significance Familial Mediterranean fever 2018-02-09 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 720 of the MEFV protein (p.Ile720Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is present in population databases (rs104895102, ExAC 0.001%). This variant has been reported in several individuals affected with familial mediterranean fever (FMF) (PMID: 11903360, 21413889). ClinVar contains an entry for this variant (Variation ID: 97499). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Integrated Genetics/Laboratory Corporation of America RCV000780406 SCV000917628 uncertain significance not specified 2018-06-04 criteria provided, single submitter clinical testing Variant summary: MEFV c.2160C>G (p.Ile720Met) results in a conservative amino acid change located in the B30.2/SPRY domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 246466 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2160C>G has been reported in the literature in numerous individuals affected with Familial Mediterranean Fever, and most of these reports are in heterozygous patients, suggesting this variant may cause the dominant form of Familial Mediterranean Fever. However, strong evidence, such as cosegregation analysis within families, was not reported in these studies. Thus, these reports do not provide unequivocal conclusions about association of the variant with Dominant Familial Mediterranean Fever. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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 VUS-possibly pathogenic until more information becomes available.
Mendelics RCV000083751 SCV001139813 uncertain significance Familial Mediterranean fever 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000083751 SCV001279827 uncertain significance Familial Mediterranean fever 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000083751 SCV000115845 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.