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NM_003331.5(TYK2):c.1825C>T (p.Arg609Ter) AND Immunodeficiency 35

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 6, 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:
RCV003832980.2

Allele description [Variation Report for NM_003331.5(TYK2):c.1825C>T (p.Arg609Ter)]

NM_003331.5(TYK2):c.1825C>T (p.Arg609Ter)

Gene:
TYK2:tyrosine kinase 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_003331.5(TYK2):c.1825C>T (p.Arg609Ter)
HGVS:
  • NC_000019.10:g.10361904G>A
  • NG_007872.1:g.23669C>T
  • NM_001385197.1:c.1825C>T
  • NM_001385198.1:c.1825C>T
  • NM_001385199.1:c.1773+174C>T
  • NM_001385200.1:c.1825C>T
  • NM_001385201.1:c.1627C>T
  • NM_001385202.1:c.1808+17C>T
  • NM_001385203.1:c.1825C>T
  • NM_001385204.1:c.1825C>T
  • NM_001385205.1:c.1735C>T
  • NM_001385206.1:c.1699C>T
  • NM_001385207.1:c.1807C>T
  • NM_001406461.1:c.1825C>T
  • NM_003331.5:c.1825C>TMANE SELECT
  • NP_001372126.1:p.Arg609Ter
  • NP_001372127.1:p.Arg609Ter
  • NP_001372129.1:p.Arg609Ter
  • NP_001372130.1:p.Arg543Ter
  • NP_001372132.1:p.Arg609Ter
  • NP_001372133.1:p.Arg609Ter
  • NP_001372134.1:p.Arg579Ter
  • NP_001372135.1:p.Arg567Ter
  • NP_001372136.1:p.Arg603Ter
  • NP_001393390.1:p.Arg609Ter
  • NP_003322.3:p.Arg609Ter
  • NP_003322.3:p.Arg609Ter
  • LRG_121t1:c.1825C>T
  • LRG_121:g.23669C>T
  • LRG_121p1:p.Arg609Ter
  • NC_000019.9:g.10472580G>A
  • NM_003331.4:c.1825C>T
Protein change:
R543*
Molecular consequence:
  • NM_001385199.1:c.1773+174C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001385202.1:c.1808+17C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001385197.1:c.1825C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001385198.1:c.1825C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001385200.1:c.1825C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001385201.1:c.1627C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001385203.1:c.1825C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001385204.1:c.1825C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001385205.1:c.1735C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001385206.1:c.1699C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001385207.1:c.1807C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406461.1:c.1825C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003331.5:c.1825C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Immunodeficiency 35 (IMD35)
Synonyms:
HIES WITH ATYPICAL MYCOBACTERIOSIS, AUTOSOMAL RECESSIVE; HYPER-IgE SYNDROME WITH ATYPICAL MYCOBACTERIOSIS, AUTOSOMAL RECESSIVE; TYK2 DEFICIENCY; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0012682; MedGen: C1969086; OMIM: 611521

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004630143Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 6, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A patient with tyrosine kinase 2 deficiency without hyper-IgE syndrome.

Kilic SS, Hacimustafaoglu M, Boisson-Dupuis S, Kreins AY, Grant AV, Abel L, Casanova JL.

J Pediatr. 2012 Jun;160(6):1055-7. doi: 10.1016/j.jpeds.2012.01.056. Epub 2012 Mar 7. Erratum in: J Pediatr. 2012 Nov;161(5):974. J Pediatr. 2013 Mar;162(3):658.

PubMed [citation]
PMID:
22402565
PMCID:
PMC3360808

Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome.

Kreins AY, Ciancanelli MJ, Okada S, Kong XF, Ramírez-Alejo N, Kilic SS, El Baghdadi J, Nonoyama S, Mahdaviani SA, Ailal F, Bousfiha A, Mansouri D, Nievas E, Ma CS, Rao G, Bernasconi A, Sun Kuehn H, Niemela J, Stoddard J, Deveau P, Cobat A, El Azbaoui S, et al.

J Exp Med. 2015 Sep 21;212(10):1641-62. doi: 10.1084/jem.20140280. Epub 2015 Aug 24.

PubMed [citation]
PMID:
26304966
PMCID:
PMC4577846
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004630143.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with TYK2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg609*) in the TYK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TYK2 are known to be pathogenic (PMID: 22402565, 26304966).

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

Last Updated: Sep 29, 2024