ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.549G>A (p.Pro183=) (rs587781035)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000126741 SCV000170253 benign not specified 2013-12-14 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757454 SCV000885686 likely benign not provided 2017-09-16 criteria provided, single submitter clinical testing The MEFV c.549G>A;p.Pro183Pro (rs587781035) variant has not been described in the medical literature, but is listed in the ClinVar database as benign (Variation ID: 138207). The variant is listed in the Genome Aggregation Database as a rare variant (10/184110 alleles). This is a silent variant, the nucleotide at this position is not well conserved across species, and computational algorithms (SpliceSiteFinder-like, MaxEntScan, NNSplice, GeneSplicer, Human Splicing Finder) predict this variant does not significantly alter splicing. Additionally, this variant is inconsistent with the pathogenic mechanism of familial Mediterranean fever. Although this variant has been described in an individual with ulcerative colitis (see link below), this variant is classified as likely benign. References: Link to MEFV database:
Invitae RCV000802334 SCV000942159 uncertain significance Familial Mediterranean fever 2019-11-15 criteria provided, single submitter clinical testing This sequence change affects codon 183 of the MEFV mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MEFV protein. This variant is present in population databases (rs587781035, ExAC 0.01%). This variant has not been reported in the literature in individuals with MEFV-related conditions. ClinVar contains an entry for this variant (Variation ID: 138207). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Illumina Clinical Services Laboratory,Illumina RCV000802334 SCV001276123 uncertain significance Familial Mediterranean fever 2018-01-12 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 RCV000126741 SCV001442695 likely benign not specified 2020-10-16 criteria provided, single submitter clinical testing

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