ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.2122C>T (p.Arg708Cys) (rs104895202)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000780404 SCV000917626 uncertain significance not specified 2018-12-24 criteria provided, single submitter clinical testing Variant summary: MEFV c.2122C>T (p.Arg708Cys) results in a non-conservative amino acid change located in the Butyrophylin-like, SPRY domain of 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 8.1e-06 in 246268 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2122C>T in individuals affected with Familial Mediterranean Fever has been reported. One publication reports in silico molecular modeling of this variant, however, does not allow convincing conclusions about the variant effect (Arakelov_2015). 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 uncertain significance.
Invitae RCV000083748 SCV001407079 uncertain significance Familial Mediterranean fever 2019-08-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 708 of the MEFV protein (p.Arg708Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 97496). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000083748 SCV000115842 not provided Familial Mediterranean fever no assertion provided not provided

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