ClinVar

Description

Variant summary: MEFV c.343C>A (p.Pro115Thr) 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 0.0004 in 247544 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in MEFV causing Familial Mediterranean Fever (0.0004 vs 0.022), allowing no conclusion about variant significance. The variant, c.343C>A, has been reported in the literature in individuals affected with Familial Mediterranean Fever (example, Ebadi_2017). This report however, does 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. Five submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified this variant as uncertain significance (n=4) (VUS, n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.