NM_001065.4(TNFRSF1A):c.679C>G (p.Leu227Val) AND TNF receptor-associated periodic fever syndrome (TRAPS)

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 3, 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:: RCV003624523.2

Allele description [Variation Report for NM_001065.4(TNFRSF1A):c.679C>G (p.Leu227Val)]

NM_001065.4(TNFRSF1A):c.679C>G (p.Leu227Val)

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.679C>G (p.Leu227Val)

HGVS:

NC_000012.12:g.6330658G>C
NG_007506.1:g.16438C>G
NM_001065.4:c.679C>GMANE SELECT
NM_001346091.2:c.355C>G
NM_001346092.2:c.220C>G
NP_001056.1:p.Leu227Val
NP_001056.1:p.Leu227Val
NP_001333020.1:p.Leu119Val
NP_001333021.1:p.Leu74Val
LRG_193t1:c.679C>G
LRG_193:g.16438C>G
LRG_193p1:p.Leu227Val
NC_000012.11:g.6439824G>C
NM_001065.3:c.679C>G
NR_144351.2:n.867C>G

Protein change:

L119V

Molecular consequence:

NM_001065.4:c.679C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001346091.2:c.355C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001346092.2:c.220C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_144351.2:n.867C>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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PREDICTED: Homo sapiens calcium channel flower domain containing 1 (CACFD1), tra...
PREDICTED: Homo sapiens calcium channel flower domain containing 1 (CACFD1), transcript variant X1, mRNA
gi|2217375307|ref|XM_011518181.3|

Nucleotide
U1 small nuclear ribonucleoprotein 70 kDa [Toxocara canis]
U1 small nuclear ribonucleoprotein 70 kDa [Toxocara canis]
gi|734562985|gb|KHN88835.1||gnl|WGS |Tcan_06982_1s

Protein
LOC129931423 [Homo sapiens]
LOC129931423 [Homo sapiens]
Gene ID:129931423

Gene
LOC130009098 [Homo sapiens]
LOC130009098 [Homo sapiens]
Gene ID:130009098

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004409233	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 3, 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

SCV004409233

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 3, 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

Citations

PubMed

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, SCV004409233.1

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 227 of the TNFRSF1A protein (p.Leu227Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TNFRSF1A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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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