Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000083740 | SCV000696057 | pathogenic | Familial Mediterranean fever | 2016-06-13 | criteria provided, single submitter | clinical testing | Variant summary: The MEFV c.2081_2083delTGA (p.Met694del) variant involves an in-frame deletion of three nucleotides. One in silico tool predicts a benign outcome for this variant. The variant is absent in 121410 control chromosomes while it was reported in several FMF patients in heterozygosity indicating a dominant inheritance. Taken together, this variant is classified as pathogenic. |
ARUP Laboratories, |
RCV000757455 | SCV000885687 | pathogenic | not provided | 2023-03-10 | criteria provided, single submitter | clinical testing | The MEFV c.2081_2083del; p.Met694del variant (rs104895091) is reported in the literature in multiple individuals and families with a clinical diagnosis of familial Mediterranean fever; individuals of northern European ancestry often had clinical symptoms without an additional pathogenic variant (Booth 2000, Booty 2009, Rowczenio 2017), whereas two individuals of Moroccan ancestry had an additional pathogenic variant consistent with autosomal recessive inheritance (Belmahi 2012). This variant is also reported in ClinVar (Variation ID: 2556), but is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant deletes a single methionine residue leaving the rest of the protein in-frame. Considering available information, this variant is classified as pathogenic. References: Belmahi L et al. MEFV mutations in Moroccan patients suffering from familial Mediterranean Fever. Rheumatol Int. 2012 Apr;32(4):981-4. PMID: 21246368. Booth DR et al. The genetic basis of autosomal dominant familial Mediterranean fever. QJM. 2000 Apr;93(4):217-21. PMID: 10787449. Booty MG et al. Familial Mediterranean fever with a single MEFV mutation: where is the second hit? Arthritis Rheum. 2009 Jun;60(6):1851-61. PMID: 19479870. Rowczenio DM et al. Autosomal dominant familial Mediterranean fever in Northern European Caucasians associated with deletion of p.M694 residue-a case series and genetic exploration. Rheumatology (Oxford). 2017 Feb;56(2):209-213. PMID: 27150194. |
Mendelics | RCV000083740 | SCV001139822 | uncertain significance | Familial Mediterranean fever | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000083740 | SCV001491922 | uncertain significance | Familial Mediterranean fever | 2022-08-19 | criteria provided, single submitter | clinical testing | This variant, c.2081_2083del, results in the deletion of 1 amino acid(s) of the MEFV protein (p.Met694del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs104895091, gnomAD 0.002%). This variant has been observed in individual(s) with Familial Mediterranean Fever (PMID: 10024914, 10787449, 19479870, 21246368, 29047407). ClinVar contains an entry for this variant (Variation ID: 2556). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects MEFV function (PMID: 33733382). 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. |
OMIM | RCV000002665 | SCV000022823 | pathogenic | Familial Mediterranean fever, autosomal dominant | 2000-04-01 | no assertion criteria provided | literature only | |
Unité médicale des maladies autoinflammatoires, |
RCV000083740 | SCV000115833 | not provided | Familial Mediterranean fever | no assertion provided | not provided | ||
Gene |
RCV000083740 | SCV000484969 | not provided | Familial Mediterranean fever | no assertion provided | literature only | ||
Natera, |
RCV000083740 | SCV001462096 | pathogenic | Familial Mediterranean fever | 2020-09-16 | no assertion criteria provided | clinical testing |