ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.926C>T (p.Thr309Met) (rs104895155)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000214115 SCV000279043 uncertain significance not specified 2016-03-11 criteria provided, single submitter clinical testing The T309M missense mutation in the MEFV gene has been reported previously in association with FMF (Chandrakasan et al., 2014). The T309M mutation has also been observed in association with FMF in an individual of Lebanese descent and has been observed at in several other individuals who were tested for suspected FMF.
Integrated Genetics/Laboratory Corporation of America RCV000214115 SCV000696082 uncertain significance not specified 2019-12-13 criteria provided, single submitter clinical testing Variant summary: MEFV c.926C>T (p.Thr309Met) results in a non-conservative amino acid change in 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 0.00057 in 247628 control chromosomes, predominantly at a frequency of 0.0028 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than expected for a pathogenic variant in MEFV causing Familial Mediterranean Fever (0.00057 vs 0.022), allowing no conclusion about variant significance. c.926C>T has been reported in the literature in patients affected with Familial Mediterranean Fever (Chandrakasan_2014), unclassified mongenic auto inflammtory disease (Omoyinmi_2017) and adult onset Still's disease (Sighart_2017) . These reports however, do not provide unequivocal conclusions about association of the variant with Familial Mediterranean Fever. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000083806 SCV001019961 likely benign Familial Mediterranean fever 2019-12-31 criteria provided, single submitter clinical testing
Mendelics RCV000083806 SCV001139865 uncertain significance Familial Mediterranean fever 2019-05-28 criteria provided, single submitter clinical testing
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000083806 SCV000115906 not provided Familial Mediterranean fever no assertion provided not provided

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