ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.1780C>T (p.Gln594Ter) (rs780770024)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000632791 SCV000753979 likely pathogenic Familial Mediterranean fever 2018-01-03 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MEFV gene (p.Gln594*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 189 amino acids of the MEFV protein. This variant is present in population databases (rs780770024, ExAC 0.002%). This variant has not been reported in the literature in individuals with MEFV-related disease. Multiple missense substitutions downstream from this truncating variant (p.Met694Val, p.Met680Ile, p.Val726Ala, p.Ala744Ser) have been determined to be pathogenic (PMID: 9781020, 10364520, 21290976, 22037353, 23907647, 9288758, 15745878, 11464238, 21600797, 21413889). This suggests that the C-terminal region is critical for MEFV protein function and that variants that disrupt this sequence may be pathogenic. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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