NM_001065.4(TNFRSF1A):c.243C>G (p.Cys81Trp) AND TNF receptor-associated periodic fever syndrome (TRAPS)

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 28, 2018
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:: RCV000083923.4

Allele description [Variation Report for NM_001065.4(TNFRSF1A):c.243C>G (p.Cys81Trp)]

NM_001065.4(TNFRSF1A):c.243C>G (p.Cys81Trp)

Gene:

TNFRSF1A:TNF receptor superfamily member 1A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.31

Genomic location:

Preferred name:

NM_001065.4(TNFRSF1A):c.243C>G (p.Cys81Trp)

HGVS:

NC_000012.12:g.6333816G>C
NG_007506.1:g.13280C>G
NM_001065.4:c.243C>GMANE SELECT
NM_001346091.2:c.-82C>G
NM_001346092.2:c.-335C>G
NP_001056.1:p.Cys81Trp
NP_001056.1:p.Cys81Trp
LRG_193t1:c.243C>G
LRG_193:g.13280C>G
LRG_193p1:p.Cys81Trp
NC_000012.11:g.6442982G>C
NM_001065.2:c.243C>G
NM_001065.3:c.243C>G
NR_144351.2:n.505C>G

Protein change:

C81W

Links:

dbSNP: rs56002980

NCBI 1000 Genomes Browser:

rs56002980

Molecular consequence:

NM_001346091.2:c.-82C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001346092.2:c.-335C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001065.4:c.243C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_144351.2:n.505C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: TNF receptor-associated periodic fever syndrome (TRAPS) (FPF)
Synonyms:: Familial Hibernian fever; Tumor necrosis factor receptor-associated periodic syndrome; TNF receptor-associated periodic syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007727; MedGen: C1275126; Orphanet: 32960; OMIM: 142680

Recent activity

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Hemagglutinin-Neuminidase protein [Respirovirus muris]
Hemagglutinin-Neuminidase protein [Respirovirus muris]
gi|152002464|dbj|BAF73489.1|

Protein
LOC4345962 [Oryza sativa Japonica Group]
LOC4345962 [Oryza sativa Japonica Group]
Gene ID:4345962

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000116035	Unité médicale des maladies autoinflammatoires, CHRU Montpellier	no classification provided	not provided	unknown	not provided
SCV000941847	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 28, 2018)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 13130484, 10199409, 12520003, 16508982, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000116035

Unité médicale des maladies autoinflammatoires, CHRU Montpellier

no classification provided

not provided

unknown

not provided

SCV000941847

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 28, 2018)

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
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes.

Aganna E, Hammond L, Hawkins PN, Aldea A, McKee SA, van Amstel HK, Mischung C, Kusuhara K, Saulsbury FT, Lachmann HJ, Bybee A, McDermott EM, La Regina M, Arostegui JI, Campistol JM, Worthington S, High KP, Molloy MG, Baker N, Bidwell JL, Castañer JL, Whiteford ML, et al.

Arthritis Rheum. 2003 Sep;48(9):2632-44.

PubMed [citation]

PMID:: 13130484

Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes.

McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW, Centola M, Mansfield E, Gadina M, Karenko L, Pettersson T, McCarthy J, Frucht DM, Aringer M, Torosyan Y, Teppo AM, Wilson M, Karaarslan HM, Wan Y, Todd I, Wood G, Schlimgen R, Kumarajeewa TR, et al.

Cell. 1999 Apr 2;97(1):133-44.

PubMed [citation]

PMID:: 10199409

See all PubMed Citations (5)

Details of each submission

From Unité médicale des maladies autoinflammatoires, CHRU Montpellier, SCV000116035.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000941847.1

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

Description

This sequence change replaces cysteine with tryptophan at codon 81 of the TNFRSF1A protein (p.Cys81Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual in the Infevers database (PMID: 12520003). ClinVar contains an entry for this variant (Variation ID: 97670). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Cys81 amino acid residue (also known as p.Cys52) in TNFRSF1A. Other variant(s) that disrupt this residue have been observed in individuals with TNFRSF1A-related conditions (PMID: 13130484, 16508982, 10199409), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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

Last Updated: Sep 29, 2024

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