ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.2038A>C (p.Met680Leu) (rs104895089)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000083732 SCV001139832 likely pathogenic Familial Mediterranean fever 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV000083732 SCV001387929 uncertain significance Familial Mediterranean fever 2019-05-31 criteria provided, single submitter clinical testing This sequence change replaces methionine with leucine at codon 680 of the MEFV protein (p.Met680Leu). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with suspected familial Mediterranean fever (PMID: 10842288, 23463692, 21246368, 17489852, 16439335). ClinVar contains an entry for this variant (Variation ID: 97480). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Met680 amino acid residue in MEFV. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23907647, 9288758, 23973724, 21623663, 21600797, 10090880, 11977178, 29080837). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 RCV000083732 SCV000115825 not provided Familial Mediterranean fever no assertion provided not provided

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