NM_000243.3(MEFV):c.704C>T (p.Ser235Leu) AND Familial Mediterranean fever

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 28, 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:: RCV001309646.9

Allele description [Variation Report for NM_000243.3(MEFV):c.704C>T (p.Ser235Leu)]

NM_000243.3(MEFV):c.704C>T (p.Ser235Leu)

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.704C>T (p.Ser235Leu)

HGVS:

NC_000016.10:g.3254364G>A
NG_007871.1:g.7264C>T
NM_000243.3:c.704C>TMANE SELECT
NM_001198536.2:c.277+1947C>T
NP_000234.1:p.Ser235Leu
LRG_190:g.7264C>T
NC_000016.9:g.3304364G>A

Protein change:

S235L

Links:

dbSNP: rs757793348

NCBI 1000 Genomes Browser:

rs757793348

Molecular consequence:

NM_001198536.2:c.277+1947C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000243.3:c.704C>T - 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
SCV001499152	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 28, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30783801, 28492532
SCV002087438	Natera, Inc.	no assertion criteria provided	Uncertain significance (Mar 25, 2021)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001499152

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 28, 2023)

germline

clinical testing

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

SCV002087438

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Mar 25, 2021)

germline

clinical testing

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

Diagnostic utility of a targeted next-generation sequencing gene panel in the clinical suspicion of systemic autoinflammatory diseases: a multi-center study.

Karacan İ, Balamir A, Uğurlu S, Aydın AK, Everest E, Zor S, Önen MÖ, Daşdemir S, Özkaya O, Sözeri B, Tufan A, Yıldırım DG, Yüksel S, Ayaz NA, Ömeroğlu RE, Öztürk K, Çakan M, Söylemezoğlu O, Şahin S, Barut K, Adroviç A, Seyahi E, et al.

Rheumatol Int. 2019 May;39(5):911-919. doi: 10.1007/s00296-019-04252-5. Epub 2019 Feb 19. Erratum in: Rheumatol Int. 2019 May;39(5):921. doi: 10.1007/s00296-019-04280-1.

PubMed [citation]

PMID:: 30783801

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001499152.4

#	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 serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 235 of the MEFV protein (p.Ser235Leu). This variant is present in population databases (rs757793348, gnomAD 0.004%). This missense change has been observed in individual(s) with systemic autoinflammatory disease (PMID: 30783801). ClinVar contains an entry for this variant (Variation ID: 1011790). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 Natera, Inc., SCV002087438.1

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

Last Updated: Sep 29, 2024

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