ClinVar Miner

Submissions for variant NM_001198536.1(MEFV):c.277+2004_277+2007dup (rs104895138)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000083796 SCV001139875 uncertain significance Familial Mediterranean fever 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000083796 SCV001338531 likely pathogenic Familial Mediterranean fever 2020-04-17 criteria provided, single submitter clinical testing Variant summary: MEFV c.761_764dupCCGC (p.Asn256ArgfsX70) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8e-06 in 251424 control chromosomes (gnomAD). c.761_764dupCCGC has been reported in the literature in individuals affected with Familial Mediterranean Fever (e.g. Infevers database, Oztuzcu_2014, Stella_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. In 2018, the experts international study group for systemic autoinflammatory diseases (INSAID) reported a provisional classification of likely pathogenic for the variant (Van Gijn_2018). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000083796 SCV001412092 uncertain significance Familial Mediterranean fever 2019-07-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn256Argfs*70) in the MEFV gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs104895138, ExAC 0.01%). This variant has been observed in individuals affected with clinical features of familial Mediterranean fever (PMID: 24469716, 30476289). ClinVar contains an entry for this variant (Variation ID: 97544). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MEFV cause disease. 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 RCV000083796 SCV000115894 not provided Familial Mediterranean fever no assertion provided not provided

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