NM_000243.3(MEFV):c.2040G>A (p.Met680Ile) AND Familial Mediterranean fever, autosomal dominant

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Mar 28, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001283820.19

Allele description [Variation Report for NM_000243.3(MEFV):c.2040G>A (p.Met680Ile)]

NM_000243.3(MEFV):c.2040G>A (p.Met680Ile)

Genes:

LOC126862264:CDK7 strongly-dependent group 2 enhancer GRCh37_chr16:3293322-3294521 [Gene]
MEFV:MEFV innate immunity regulator, pyrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_000243.3(MEFV):c.2040G>A (p.Met680Ile)

Other names:

MEFV, MET680ILE, 2040G-A; M680I

HGVS:

NC_000016.10:g.3243447C>T
NG_007871.1:g.18181G>A
NM_000243.3:c.2040G>AMANE SELECT
NM_001198536.2:c.*244G>A
NP_000234.1:p.Met680Ile
NP_000234.1:p.Met680Ile
LRG_190t1:c.2040G>A
LRG_190:g.18181G>A
LRG_190p1:p.Met680Ile
NC_000016.9:g.3293447C>T
NM_000243.2:c.2040G>A
O15553:p.Met680Ile
c.2040G>A (p.Met680Ile)

Protein change:

MET680ILE

Links:

UniProtKB: O15553#VAR_028343; OMIM: 608107.0013; dbSNP: rs28940580

NCBI 1000 Genomes Browser:

rs28940580

Molecular consequence:

NM_001198536.2:c.*244G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000243.3:c.2040G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial Mediterranean fever, autosomal dominant
Synonyms:: FMF, AUTOSOMAL DOMINANT; Dominant Familial Mediterranean Fever
Identifiers:: MONDO: MONDO:0007601; MedGen: C1851347; Orphanet: 342; OMIM: 134610

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001469229	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	no assertion criteria provided	Pathogenic (Jun 7, 2020)	germline	clinical testing
SCV004194412	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 28, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005088834	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 4, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001469229

Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City

no assertion criteria provided

Pathogenic
(Jun 7, 2020)

germline

clinical testing

SCV004194412

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 28, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005088834

Breakthrough Genomics, Breakthrough Genomics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 4, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City, SCV001469229.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital, SCV001984411.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004194412.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Breakthrough Genomics, Breakthrough Genomics, SCV005088834.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant has been observed in individuals with familial Mediterranean fever in heterozygous/compound heterozygous/homozygous state [PMID: 9288758, 10090880, 11977178, 21623663, 23907647, 23973724, 29080837]. Functional studies demonstrate that the variant results in decreased binding of caspase-1 compared to wild-type [PMID: 16785446].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001984411	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	flagged submission Reason: This record appears to be redundant with a more recent record from the same submitter. Notes: SCV001984411 appears to be redundant with SCV002818286. (ACMG Guidelines, 2015)	Pathogenic (Jul 16, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001984411

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

flagged submission

Reason: This record appears to be redundant with a more recent record from the same submitter.

Notes: SCV001984411 appears to be redundant with SCV002818286.

(ACMG Guidelines, 2015)

Pathogenic
(Jul 16, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Last Updated: Oct 13, 2024

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Relating variation to medicine