NM_000243.3(MEFV):c.407G>A (p.Gly136Glu) AND Familial Mediterranean fever

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Feb 8, 2023
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:: RCV000688336.9

Allele description [Variation Report for NM_000243.3(MEFV):c.407G>A (p.Gly136Glu)]

NM_000243.3(MEFV):c.407G>A (p.Gly136Glu)

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.407G>A (p.Gly136Glu)

HGVS:

NC_000016.10:g.3254661C>T
NG_007871.1:g.6967G>A
NM_000243.3:c.407G>AMANE SELECT
NM_001198536.2:c.277+1650G>A
NP_000234.1:p.Gly136Glu
NP_000234.1:p.Gly136Glu
LRG_190t1:c.407G>A
LRG_190:g.6967G>A
LRG_190p1:p.Gly136Glu
NC_000016.9:g.3304661C>T
NM_000243.2:c.407G>A

Protein change:

G136E

Links:

dbSNP: rs876660989

NCBI 1000 Genomes Browser:

rs876660989

Molecular consequence:

NM_001198536.2:c.277+1650G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000243.3:c.407G>A - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000815942	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 20, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23862117, 28492532
SCV001139892	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV003802396	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 8, 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

SCV000815942

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 20, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001139892

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Uncertain significance
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV003802396

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 8, 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	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

Mediterranean Fever gene analysis in the azeri turk population with familial mediterranean Fever: evidence for new mutations associated with disease.

Mohammadnejad L, Farajnia S.

Cell J. 2013 Summer;15(2):152-9. Epub 2013 Jul 2.

PubMed [citation]

PMID:: 23862117
PMCID:: PMC3712776

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000815942.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces glycine with glutamic acid at codon 136 of the MEFV protein (p.Gly136Glu). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with familial mediterranean fever (PMID: 23862117). ClinVar contains an entry for this variant (Variation ID: 234351). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

#	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

From Mendelics, SCV001139892.1

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

From Genome-Nilou Lab, SCV003802396.1

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

Last Updated: Jul 29, 2023

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