NM_001065.4(TNFRSF1A):c.197C>T (p.Thr66Ile) AND TNF receptor-associated periodic fever syndrome (TRAPS)

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 9, 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:: RCV000083911.4

Allele description [Variation Report for NM_001065.4(TNFRSF1A):c.197C>T (p.Thr66Ile)]

NM_001065.4(TNFRSF1A):c.197C>T (p.Thr66Ile)

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.197C>T (p.Thr66Ile)

HGVS:

NC_000012.12:g.6333862G>A
NG_007506.1:g.13234C>T
NM_001065.4:c.197C>TMANE SELECT
NM_001346091.2:c.-128C>T
NM_001346092.2:c.-381C>T
NP_001056.1:p.Thr66Ile
LRG_193:g.13234C>T
NC_000012.11:g.6443028G>A
NM_001065.2:c.197C>T
NR_144351.2:n.459C>T

Protein change:

T66I

Links:

dbSNP: rs104895243

NCBI 1000 Genomes Browser:

rs104895243

Molecular consequence:

NM_001346091.2:c.-128C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001346092.2:c.-381C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001065.4:c.197C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_144351.2:n.459C>T - 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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A-kinase anchor protein 17A isoform 1 [Homo sapiens]
A-kinase anchor protein 17A isoform 1 [Homo sapiens]
gi|41152097|ref|NP_005079.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000116021	Unité médicale des maladies autoinflammatoires, CHRU Montpellier	no classification provided	not provided	unknown	not provided
SCV004295828	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 9, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 13130484, 23965844, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000116021

Unité médicale des maladies autoinflammatoires, CHRU Montpellier

no classification provided

not provided

unknown

not provided

SCV004295828

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 9, 2023)

germline

clinical testing

PubMed (3)
[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

The phenotype of TNF receptor-associated autoinflammatory syndrome (TRAPS) at presentation: a series of 158 cases from the Eurofever/EUROTRAPS international registry.

Lachmann HJ, Papa R, Gerhold K, Obici L, Touitou I, Cantarini L, Frenkel J, Anton J, Kone-Paut I, Cattalini M, Bader-Meunier B, Insalaco A, Hentgen V, Merino R, Modesto C, Toplak N, Berendes R, Ozen S, Cimaz R, Jansson A, Brogan PA, Hawkins PN, et al.

Ann Rheum Dis. 2014 Dec;73(12):2160-7. doi: 10.1136/annrheumdis-2013-204184. Epub 2013 Aug 21.

PubMed [citation]

PMID:: 23965844
PMCID:: PMC4251160

See all PubMed Citations (3)

Details of each submission

From Unité médicale des maladies autoinflammatoires, CHRU Montpellier, SCV000116021.1

#	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, SCV004295828.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 66 of the TNFRSF1A protein (p.Thr66Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with TNF receptor-associated periodic fever syndrome (PMID: 13130484, 23965844). This variant is also known as T37I. ClinVar contains an entry for this variant (Variation ID: 97658). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TNFRSF1A protein function. 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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