ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.343C>A (p.Pro115Thr) (rs147557169)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000221844 SCV000279025 uncertain significance not provided 2017-04-07 criteria provided, single submitter clinical testing The P115T variant has been reported in a symptomatic patient with a periodic fever syndrome. The P115T variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, the P115T variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is variable across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant
Illumina Clinical Services Laboratory,Illumina RCV000083246 SCV000396783 uncertain significance Familial Mediterranean fever 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193206 SCV001361912 uncertain significance not specified 2019-07-11 criteria provided, single submitter clinical testing 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 (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. Two 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. Based on the evidence outlined above, the variant was classified as uncertain significance until additional information becomes available.
Invitae RCV000083246 SCV001640092 likely benign Familial Mediterranean fever 2020-09-29 criteria provided, single submitter clinical testing
Medical Biology Lab, Gaziantep University RCV000083246 SCV000115320 not provided Familial Mediterranean fever no assertion provided not provided
Natera, Inc. RCV000083246 SCV001457157 uncertain significance Familial Mediterranean fever 2020-09-16 no assertion criteria provided clinical testing

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