NM_000243.3(MEFV):c.1459G>C (p.Val487Leu) AND Familial Mediterranean fever, autosomal dominant

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 27, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003150813.1

Allele description [Variation Report for NM_000243.3(MEFV):c.1459G>C (p.Val487Leu)]

NM_000243.3(MEFV):c.1459G>C (p.Val487Leu)

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.1459G>C (p.Val487Leu)

Other names:

p.Val487Leu

HGVS:

NC_000016.10:g.3247144C>G
NG_007871.1:g.14484G>C
NM_000243.3:c.1459G>CMANE SELECT
NM_001198536.2:c.826G>C
NP_000234.1:p.Val487Leu
NP_000234.1:p.Val487Leu
NP_001185465.2:p.Val276Leu
LRG_190t1:c.1459G>C
LRG_190:g.14484G>C
LRG_190p1:p.Val487Leu
NC_000016.9:g.3297144C>G
NM_000243.2:c.1459G>C

Protein change:

V276L

Links:

dbSNP: rs104895100

NCBI 1000 Genomes Browser:

rs104895100

Molecular consequence:

NM_000243.3:c.1459G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001198536.2:c.826G>C - 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
SCV003839079	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 27, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 29178647, 29599418, 29735907, 31411330, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003839079

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 27, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Citations

PubMed

Comprehensive analysis of mutations in the MEFV gene reveal that the location and not the substitution type determines symptom severity in FMF.

Moradian MM, Babikyan D, Banoian D, Hayrapetyan H, Manvelyan H, Avanesian N, Sarkisian T.

Mol Genet Genomic Med. 2017 Nov;5(6):742-750. doi: 10.1002/mgg3.336. Epub 2017 Oct 9.

PubMed [citation]

PMID:: 29178647
PMCID:: PMC5702578

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, Ceccherini I, Shinar Y, Carbo EC, Slofstra M, Arostegui JI, Sarrabay G, Rowczenio D, Omoyımnı E, Balci-Peynircioglu B, Hoffman HM, Milhavet F, Swertz MA, Touitou I.

J Med Genet. 2018 Aug;55(8):530-537. doi: 10.1136/jmedgenet-2017-105216. Epub 2018 Mar 29.

PubMed [citation]

PMID:: 29599418

See all PubMed Citations (5)

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV003839079.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This MEFV missense variant has been reported in an individual suspected to have familial Mediterranean fever. The variant (rs104895100) is present in a large population dataset (gnomAD v3.1.2: 339/152196 total alleles; 0.223%; 3 homozygotes), and has been reported in ClinVar2 (Variation ID 378132). Two bioinformatic tools queried predict that this substitution would be tolerated, but these algorithms have low specificity, especially for predicting gain of function or dominant negative variants. The valine residue at this position is evolutionarily conserved across very few of the species assessed, and most of the species have leucine at this position. We consider the clinical significance of c.1459G>C; p.Val487Leu in MEFV to be uncertain at this time.

#	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: Sep 29, 2024

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Relating variation to medicine