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NM_003265.3(TLR3):c.1660C>T (p.Pro554Ser) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 19, 2019
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:
RCV000826059.4

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]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000967553Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Uncertain significance
(Feb 19, 2019) 		germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown21not providednot providednot providedclinical testing

Citations

PubMed

TLR3 deficiency in patients with herpes simplex encephalitis.

Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, Romero P, Segal D, Sancho-Shimizu V, Lorenzo L, Puel A, Picard C, Chapgier A, Plancoulaine S, Titeux M, Cognet C, von Bernuth H, Ku CL, Casrouge A, Zhang XX, Barreiro L, Leonard J, Hamilton C, et al.

Science. 2007 Sep 14;317(5844):1522-7.

PubMed [citation]
PMID:
17872438

A role for Toll-like receptor 3 variants in host susceptibility to enteroviral myocarditis and dilated cardiomyopathy.

Gorbea C, Makar KA, Pauschinger M, Pratt G, Bersola JL, Varela J, David RM, Banks L, Huang CH, Li H, Schultheiss HP, Towbin JA, Vallejo JG, Bowles NE.

J Biol Chem. 2010 Jul 23;285(30):23208-23. doi: 10.1074/jbc.M109.047464. Epub 2010 May 14.

PubMed [citation]
PMID:
20472559
PMCID:
PMC2906314
See all PubMed Citations (9)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967553.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (9)

Description

The p.Pro554Ser variant in TLR3 has been reported in 2 heterozygous and 1 compound heterozygous individuals with herpes simplex encephalitis (HSE), and 1 heterozygous proband with enteroviral myocarditis (Zhang 2007, Gorbea 2010, Guo 2011). However, it has also been identified in multiple unaffected family members (Zhang 2007, Guo 2011) and in 0.07% (91/129040) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has been reported as a variant of uncertain significance in ClinVar (Variation ID 6662). Computational prediction tools and conservation analysis suggest that the p.Pro554Ser variant may impact the protein, though this information is not predictive enough to determine pathogenicity. Furthermore, in vitro functional assays have produced conflicting results regarding the impact of this variant on protein function (Zhang 2007, Wang 2009, Gorbea 2010, Qi 2010, Guo 2011). Finally, although TLR3 variants have been reported in association with HSE, this gene-disease relationship has not been definitively established. In summary, the clinical significance of the p.Pro554Ser variant is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided2not provided1not provided

Last Updated: Oct 13, 2024