NM_000243.3(MEFV):c.2177T>C (p.Val726Ala) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 30, 2021
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:: RCV001535867.11

Allele description

NM_000243.3(MEFV):c.2177T>C (p.Val726Ala)

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.2177T>C (p.Val726Ala)

HGVS:

NC_000016.10:g.3243310A>G
NG_007871.1:g.18318T>C
NM_000243.3:c.2177T>CMANE SELECT
NM_001198536.2:c.*381T>C
NP_000234.1:p.Val726Ala
NP_000234.1:p.Val726Ala
LRG_190t1:c.2177T>C
LRG_190:g.18318T>C
LRG_190p1:p.Val726Ala
NC_000016.9:g.3293310A>G
NM_000243.2:c.2177T>C
O15553:p.Val726Ala
c.2177T>C (p.Val726Ala)

Protein change:

V726A; VAL726ALA

Links:

UniProtKB: O15553#VAR_009065; OMIM: 608107.0003; dbSNP: rs28940579

NCBI 1000 Genomes Browser:

rs28940579

Molecular consequence:

NM_001198536.2:c.*381T>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000243.3:c.2177T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial Mediterranean fever (FMF)
Synonyms:: POLYSEROSITIS, FAMILIAL PAROXYSMAL; POLYSEROSITIS, RECURRENT; Periodic peritonitis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018088; MedGen: C0031069; Orphanet: 342; OMIM: 249100

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

Name:: Acute febrile neutrophilic dermatosis (AFND)
Synonyms:: Sweet Syndrome; Gomm Button disease
Identifiers:: MONDO: MONDO:0011959; MedGen: C0085077; Orphanet: 3243; OMIM: 608068

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001752485	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 30, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003920191	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 30, 2021)	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

SCV001752485

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 30, 2021)

unknown

clinical testing

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

SCV003920191

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 30, 2021)

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	unknown	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 Fulgent Genetics, Fulgent Genetics, SCV001752485.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003920191.1

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

Description

MEFV NM_000243 exon 10 p.Val726Ala (c.2177T>C): This variant is a well established, common pathogenic variant for Familial Mediterranean Fever. This variant has been reported in several publications, including a Genereviews entry describing this variant as disease causing (International FMF Consortium 1997 PMID:8288758, Moradian 2014 PMID:23907647, Shothat 2016 PMID:20301405). This variant is present in 4% (402/10152) of Ashkenazi Jewish alleles including 9 homozygotes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rsrs28940579). Please note, disease causing variants may be present in control databases at low frequencies, reflective of the general population, carrier status and/or variable expressivity. This variant is present in ClinVar, with several labs classifying this variant as pathogenic (Variation ID:2540). In summary, this variant is classified as pathogenic based on the data above.

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

Last Updated: May 1, 2024

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