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NM_000243.3(MEFV):c.800C>T (p.Thr267Ile)

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Interpretation:
Conflicting interpretations of pathogenicity​

Pathogenic(1);Uncertain significance(4)

Review status:
criteria provided, conflicting interpretations
Submissions:
11 (Most recent: Sep 23, 2021)
Last evaluated:
Nov 1, 2020
Accession:
VCV000002544.19
Variation ID:
2544
Description:
single nucleotide variant
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NM_000243.3(MEFV):c.800C>T (p.Thr267Ile)

Allele ID
17583
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
16p13.3
Genomic location
16: 3254268 (GRCh38) GRCh38 UCSC
16: 3304268 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
O15553:p.Thr267Ile
LRG_190:g.7360C>T
LRG_190t1:c.800C>T LRG_190p1:p.Thr267Ile
... more HGVS
Protein change
T267I
Other names
-
Canonical SPDI
NC_000016.10:3254267:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (A)

Allele frequency
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00010
The Genome Aggregation Database (gnomAD), exomes 0.00016
The Genome Aggregation Database (gnomAD) 0.00006
Exome Aggregation Consortium (ExAC) 0.00014
Links
ClinGen: CA280101
UniProtKB: O15553#VAR_009054
OMIM: 608107.0007
dbSNP: rs104895081
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 5 criteria provided, multiple submitters, no conflicts Oct 19, 2020 RCV000002653.11
Uncertain significance 3 criteria provided, single submitter Nov 1, 2020 RCV000996177.5
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Jan 13, 2020 RCV000991330.3
not provided 1 no assertion provided - RCV001535446.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MEFV No evidence available No evidence available GRCh38
GRCh37
691 739

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Familial Mediterranean fever
Allele origin: unknown
Mendelics
Accession: SCV001139873.1
Submitted: (Oct 22, 2019)
Evidence details
Uncertain significance
(Nov 01, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001150755.7
Submitted: (Jul 04, 2021)
Evidence details
Uncertain significance
(Jan 13, 2020)
criteria provided, single submitter
Method: clinical testing
not specified
(Autosomal recessive inheritance)
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696080.2
Submitted: (Jan 14, 2020)
Evidence details
Publications
PubMed (12)
30887796
29599418
22661645
28386255
20485448
21413889
Comment:
MEFV c.800C>T (p.Thr267Ile) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of … (more)
Pathogenic
(Mar 25, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001156580.1
Submitted: (Aug 05, 2019)
Evidence details
Comment:
The MEFV c.800C>T; p.Thr267Ile variant (rs104895081) has been published in the literature in individuals with familial Mediterranean fever (FMF) or juvenile idiopathic arthritis, with or … (more)
Uncertain significance
(Oct 19, 2020)
criteria provided, single submitter
Method: clinical testing
Familial Mediterranean fever
Allele origin: germline
Invitae
Accession: SCV000753975.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (11)
Comment:
This sequence change replaces threonine with isoleucine at codon 267 of the MEFV protein (p.Thr267Ile). The threonine residue is weakly conserved and there is a … (more)
Uncertain significance
(May 14, 2018)
no assertion criteria provided
Method: clinical testing
Familial Mediterranean fever
Allele origin: unknown
Counsyl
Accession: SCV001132247.1
Submitted: (Aug 05, 2019)
Evidence details
Publications
PubMed (14)
Likely pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001931647.1
Submitted: (Sep 23, 2021)
Evidence details
Pathogenic
(Aug 01, 1998)
no assertion criteria provided
Method: literature only
FAMILIAL MEDITERRANEAN FEVER
Allele origin: germline
OMIM
Accession: SCV000022811.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Likely pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001963806.2
Submitted: (Sep 21, 2021)
Evidence details
not provided
(-)
no assertion provided
Method: not provided
Familial Mediterranean fever
Allele origin: not provided
Unité médicale des maladies autoinflammatoires, CHRU Montpellier
Accession: SCV000115896.1
Submitted: (Jun 07, 2010)
Evidence details
not provided
(-)
no assertion provided
Method: phenotyping only
Familial mediterranean fever, autosomal dominant
Allele origin: unknown
GenomeConnect - Invitae Patient Insights Network
Accession: SCV001749357.1
Submitted: (Apr 26, 2021)
Evidence details
Comment:
Variant interpreted as Uncertain significance and reported on 09-24-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
The distribution of MEFV mutations in Turkish FMF patients: multicenter study representing results of Anatolia Yaşar Bilge Ş Turkish journal of medical sciences 2019 PMID: 30887796
New workflow for classification of genetic variants' pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID). Van Gijn ME Journal of medical genetics 2018 PMID: 29599418
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management. Özen S Frontiers in immunology 2017 PMID: 28386255
Familial Mediterranean fever gene mutations in north-eastern part of Anatolia with special respect to rare mutations. Dogan H Gene 2015 PMID: 26003477
The spectrum of MEFV gene mutations and genotypes in Van province, the eastern region of Turkey, and report of a novel mutation (R361T). Coşkun S Gene 2015 PMID: 25703702
Screening of common and novel familial mediterranean fever mutations in south-east part of Turkey. Oztuzcu S Molecular biology reports 2014 PMID: 24469716
MEFV mutations affecting pyrin amino acid 577 cause autosomal dominant autoinflammatory disease. Stoffels M Annals of the rheumatic diseases 2014 PMID: 23505238
MEFV gene mutations in Turkish children with juvenile idiopathic arthritis. Comak E European journal of pediatrics 2013 PMID: 23588594
Familial Mediterranean fever in Germany: epidemiological, clinical, and genetic characteristics of a pediatric population. Lainka E European journal of pediatrics 2012 PMID: 22903357
Frequency of alterations in the MEFV gene and clinical signs in familial Mediterranean fever in Central Anatolia, Turkey. Ceylan GG Genetics and molecular research : GMR 2012 PMID: 22614345
Evaluation of the current disease severity scores in paediatric FMF: is it necessary to develop a new one? Kalkan G Rheumatology (Oxford, England) 2012 PMID: 22190688
Comprehensive analysis of a large-scale screen for MEFV gene mutations: do they truly provide a "heterozygote advantage" in Turkey? Berdeli A Genetic testing and molecular biomarkers 2011 PMID: 21413889
Molecular evaluation of 458 patients referred with a clinical diagnosis of familial Mediterranean fever in Scandinavia. Cornelius N Rheumatology international 2011 PMID: 20721559
Mediterranean fever (MEFV) gene mutation frequency is not increased in adults with rheumatic heart disease. Simsek I Clinical rheumatology 2011 PMID: 20645115
Genotype-phenotype studies in a large cohort of Armenian patients with familial Mediterranean fever suggest clinical disease with heterozygous MEFV mutations. Moradian MM Journal of human genetics 2010 PMID: 20485448
MEFV alterations and population genetics analysis in a large cohort of Greek patients with familial Mediterranean fever. Giaglis S Clinical genetics 2007 PMID: 17489852
Increased frequency of mutations in the gene responsible for familial Mediterranean fever (MEFV) in a cohort of patients with ulcerative colitis: evidence for a potential disease-modifying effect? Giaglis S Digestive diseases and sciences 2006 PMID: 16614989
Familial Mediterranean fever (FMF) in Lebanon and Jordan: a population genetics study and report of three novel mutations. Medlej-Hashim M European journal of medical genetics 2005 PMID: 16378925
Genetic screening of familial Mediterranean fever mutations in the Palestinian population. Ayesh SK Saudi medical journal 2005 PMID: 15951859
The west side story: MEFV haplotype in Spanish FMF patients and controls, and evidence of high LD and a recombination "hot-spot" at the MEFV locus. Aldea A Human mutation 2004 PMID: 15024744
Familial Mediterranean fever in Lebanon: mutation spectrum, evidence for cases in Maronites, Greek orthodoxes, Greek catholics, Syriacs and Chiites and for an association between amyloidosis and M694V and M694I mutations. Mansour I European journal of human genetics : EJHG 2001 PMID: 11175300
Genetic screening of fourteen mutations in Jordanian familial Mediterranean fever patients. Medlej-Hashim M Human mutation 2000 PMID: 10737992
Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF). Bernot A Human molecular genetics 1998 PMID: 9668175
20485448 - - - -
21413889 - - - -
22661645 - - - -
28386255 - - - -
29599418 - - - -
30887796 - - - -

Text-mined citations for rs104895081...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 20, 2021