ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.443A>T (p.Glu148Val) (rs104895076)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000415966 SCV000493691 uncertain significance not provided 2016-07-31 criteria provided, single submitter clinical testing
GeneDx RCV000216721 SCV000279032 uncertain significance not specified 2015-09-29 criteria provided, single submitter clinical testing The E148V variant of unknown significance has been previously published in association with familial Mediterranean fever and juvenile idopathic arthritis (Sever et al., 2012; Comak et al., 2013). It was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. E148V is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to glutamic acid are tolerated across species. However, in-silico analysis predicts this variant is probably damaging to the protein structure/function. Missense pathogenic variants at the same codon (E148Q) and in nearby residues (S141I, R143P) have also been reported in the Human Gene Pathogenic variant Database in association with familial Mediterranean fever (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Integrated Genetics/Laboratory Corporation of America RCV000002663 SCV000052849 uncertain significance Familial Mediterranean fever 2015-10-02 no assertion criteria provided clinical testing
OMIM RCV000002663 SCV000022821 pathogenic Familial Mediterranean fever 2002-01-01 no assertion criteria provided literature only
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000002663 SCV000115872 not provided Familial Mediterranean fever no assertion provided not provided

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