NM_001065.4(TNFRSF1A):c.176G>C (p.Cys59Ser) AND TNF receptor-associated periodic fever syndrome (TRAPS)

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 9, 2020
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:: RCV000013135.32

Allele description [Variation Report for NM_001065.4(TNFRSF1A):c.176G>C (p.Cys59Ser)]

NM_001065.4(TNFRSF1A):c.176G>C (p.Cys59Ser)

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.176G>C (p.Cys59Ser)

Other names:

C30S

HGVS:

NC_000012.12:g.6334108C>G
NG_007506.1:g.12988G>C
NM_001065.4:c.176G>CMANE SELECT
NM_001346091.2:c.-131-243G>C
NM_001346092.2:c.-402G>C
NP_001056.1:p.Cys59Ser
NP_001056.1:p.Cys59Ser
LRG_193t1:c.176G>C
LRG_193:g.12988G>C
LRG_193p1:p.Cys59Ser
NC_000012.11:g.6443274C>G
NM_001065.2:c.176G>C
NM_001065.3:c.176G>C
NR_144351.2:n.438G>C
P19438:p.Cys59Ser

Protein change:

C59S; CYS30SER

Links:

UniProtKB: P19438#VAR_019302; OMIM: 191190.0008; dbSNP: rs104895223

NCBI 1000 Genomes Browser:

rs104895223

Molecular consequence:

NM_001346092.2:c.-402G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001346091.2:c.-131-243G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001065.4:c.176G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_144351.2:n.438G>C - 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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serine/threonine-protein kinase ULK4 isoform 1 [Homo sapiens]
serine/threonine-protein kinase ULK4 isoform 1 [Homo sapiens]
gi|151301204|ref|NP_060356.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000033382	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2001)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 10902757, 11443543
SCV000116013	Unité médicale des maladies autoinflammatoires, CHRU Montpellier	no classification provided	not provided	unknown	not provided
SCV001237279	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 9, 2020)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 11722598, 15216558, 18408954, 10199409, 16684962, 10902757, 20576331, 11443543, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000033382

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2001)

germline

literature only

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

SCV000116013

Unité médicale des maladies autoinflammatoires, CHRU Montpellier

no classification provided

not provided

unknown

not provided

SCV001237279

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 9, 2020)

germline

clinical testing

PubMed (9)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
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

Periodic fever (TRAPS) caused by mutations in the TNFalpha receptor 1 (TNFRSF1A) gene of three German patients.

Rösen-Wolff A, Kreth HW, Hofmann S, Höhne K, Heubner G, Möbius D, Zintl F, Gahr M, Roesler J.

Eur J Haematol. 2001 Aug;67(2):105-9.

PubMed [citation]

PMID:: 11722598

A novel mutation of tumor necrosis factor receptor alpha type 1 associated with TRAPS and amyloidosis.

Broeders EN, Abramowicz D, Abramowicz MJ, Parma J.

Am J Med Genet A. 2004 Jul 30;128A(3):331. No abstract available.

PubMed [citation]

PMID:: 15216558

See all PubMed Citations (9)

Details of each submission

From OMIM, SCV000033382.2

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

Description

Dode et al. (2000) observed the cys30-to-ser (C30S) mutation in a French family with periodic fever (142680); Aksentijevich et al. (2001) found the same mutation in an Irish American family with 3 affected members. The cys30-to-arg mutation (191190.0003) in the same codon had been previously reported.

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

From Unité médicale des maladies autoinflammatoires, CHRU Montpellier, SCV000116013.1

#	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, SCV001237279.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys59 amino acid residue in TNFRSF1A. Other variant(s) that disrupt this residue have been observed in individuals with TNFRSF1A-related conditions (PMID: 11722598, 15216558, 18408954, 10199409), which suggests that this may be a clinically significant amino acid residue. This variant has been reported to affect TNFRSF1A protein function (PMID: 16684962). This variant has been observed in several individuals and families affected with TNF receptor-associated periodic syndrome (TRAPS) (PMID: 10902757, 20576331, 11443543). This variant is also known as p.C30S in the literature. ClinVar contains an entry for this variant (Variation ID: 12342). This variant is present in population databases (rs104895223, ExAC 0.01%). This sequence change replaces cysteine with serine at codon 59 of the TNFRSF1A protein (p.Cys59Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine.

#	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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