ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.1016C>T (p.Ser339Phe) (rs104895157)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000366739 SCV000329420 uncertain significance not provided 2017-11-24 criteria provided, single submitter clinical testing The S339F variant of uncertain significance in the MEFV gene has been previously reported in association with FMF (Federici et al., 2012). It was not observed at any significant frequency in approximately 6,400 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project. The S339F variant 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. However, this substitution occurs at a position that is not conserved and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000030169 SCV000940571 uncertain significance Familial Mediterranean fever 2019-11-20 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 339 of the MEFV protein (p.Ser339Phe). The serine residue is weakly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs104895157, ExAC 0.03%). This variant has been observed in individuals affected with familial Mediterranean fever (PMID: 22580583, 21413889, 22903357). ClinVar contains an entry for this variant (Variation ID: 36497). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001441 SCV001158679 uncertain significance not specified 2019-02-15 criteria provided, single submitter clinical testing The MEFV c.1016C>T; p.Ser339Phe (rs104895157) is reported in the Infevers database in an individual without a described phenotype (see link below). The variant is reported in the ClinVar database (Variation ID: 36497) and in the general population with an overall allele frequency of 0.02% (50/279412 alleles) in the Genome Aggregation Database. The serine at this position is moderately conserved and computational analyses (SIFT: tolerated, PolyPhen-2: possibly damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the variant is uncertain at this time. References: Link to Infevers database: https://infevers.umai-montpellier.fr/web/search.php?n=1
Illumina Clinical Services Laboratory,Illumina RCV000030169 SCV001279958 uncertain significance Familial Mediterranean fever 2017-06-14 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Integrated Genetics/Laboratory Corporation of America RCV000030169 SCV000052827 uncertain significance Familial Mediterranean fever 2015-10-02 no assertion criteria provided clinical testing
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000030169 SCV000115765 not provided Familial Mediterranean fever no assertion provided not provided

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