NM_003265.3(TLR3):c.1660C>T (p.Pro554Ser) AND Herpes simplex encephalitis, susceptibility to, 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 31, 2024
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:: RCV000647016.10

Allele description [Variation Report for NM_003265.3(TLR3):c.1660C>T (p.Pro554Ser)]

NM_003265.3(TLR3):c.1660C>T (p.Pro554Ser)

Gene:

TLR3:toll like receptor 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q35.1

Genomic location:

Preferred name:

NM_003265.3(TLR3):c.1660C>T (p.Pro554Ser)

HGVS:

NC_000004.12:g.186083346C>T
NG_007278.1:g.19192C>T
NM_003265.3:c.1660C>TMANE SELECT
NP_003256.1:p.Pro554Ser
NP_003256.1:p.Pro554Ser
LRG_117t1:c.1660C>T
LRG_117:g.19192C>T
LRG_117p1:p.Pro554Ser
NC_000004.11:g.187004500C>T
NM_003265.2:c.1660C>T
O15455:p.Pro554Ser

Protein change:

P554S; PRO554SER

Links:

UniProtKB: O15455#VAR_054887; OMIM: 603029.0001; dbSNP: rs121434431

NCBI 1000 Genomes Browser:

rs121434431

Molecular consequence:

NM_003265.3:c.1660C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Herpes simplex encephalitis, susceptibility to, 1 (IIAE1)
Synonyms:: Herpes simplex encephalitis 1; ENCEPHALOPATHY, ACUTE, INFECTION-INDUCED (HERPES-SPECIFIC), SUSCEPTIBILITY TO, 1
Identifiers:: MONDO: MONDO:0024563; MedGen: C2750180; Orphanet: 1930; OMIM: 610551

Recent activity

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translatiom enlongation factor 1 alpha, partial [Diaporthe novem]
translatiom enlongation factor 1 alpha, partial [Diaporthe novem]
gi|1995624982|gb|QSG01172.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000768802	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 31, 2024)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 21911422, 33174085, 34813006, 17872438, 19625408, 20472559, 20855885, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000768802

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 31, 2024)

germline

clinical testing

PubMed (8)
[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

Citations

PubMed

Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity.

Guo Y, Audry M, Ciancanelli M, Alsina L, Azevedo J, Herman M, Anguiano E, Sancho-Shimizu V, Lorenzo L, Pauwels E, Philippe PB, Pérez de Diego R, Cardon A, Vogt G, Picard C, Andrianirina ZZ, Rozenberg F, Lebon P, Plancoulaine S, Tardieu M, Valérie Doireau, Jouanguy E, et al.

J Exp Med. 2011 Sep 26;208(10):2083-98. doi: 10.1084/jem.20101568. Epub 2011 Sep 12.

PubMed [citation]

PMID:: 21911422
PMCID:: PMC3182056

Pathogenic TLR3 Variant in a Patient with Recurrent Herpes Simplex Virus 1-Triggered Erythema Multiforme.

Bucciol G, Delafontaine S, Moens L, Corveleyn A, Morren MA, Meyts I.

J Clin Immunol. 2021 Jan;41(1):280-282. doi: 10.1007/s10875-020-00907-2. Epub 2020 Nov 10. No abstract available.

PubMed [citation]

PMID:: 33174085

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000768802.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 554 of the TLR3 protein (p.Pro554Ser). This variant is present in population databases (rs121434431, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with herpes simplex encephalitis, severe influenza pneumonia, and/or recurrent herpes simplex virus 1‚Äìtriggered erythema multiforme (PMID: 17872438, 21911422, 33174085, 34813006). ClinVar contains an entry for this variant (Variation ID: 6662). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TLR3 function (PMID: 17872438, 19625408, 20472559, 20855885). 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: Oct 8, 2024

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