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NM_003331.5(TYK2):c.658C>T (p.Arg220Cys) AND Immunodeficiency 35

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 24, 2020
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:
RCV001053900.7

Allele description [Variation Report for NM_003331.5(TYK2):c.658C>T (p.Arg220Cys)]

NM_003331.5(TYK2):c.658C>T (p.Arg220Cys)

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.658C>T (p.Arg220Cys)
HGVS:
  • NC_000019.10:g.10365870G>A
  • NG_007872.1:g.19703C>T
  • NM_003331.5:c.658C>TMANE SELECT
  • NP_003322.3:p.Arg220Cys
  • LRG_121t1:c.658C>T
  • LRG_121:g.19703C>T
  • NC_000019.9:g.10476546G>A
  • NM_003331.4:c.658C>T
Protein change:
R220C
Links:
dbSNP: rs557436288
NCBI 1000 Genomes Browser:
rs557436288
Molecular consequence:
  • NM_003331.5:c.658C>T - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

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    Nucleotide
  • Globosides
    Globosides
    Glycosphingolipids containing N-acetylglucosamine (paragloboside) or N-acetylgalactosamine (globoside). Globoside is the P antigen on erythrocytes and paragloboside is an inte...<br/>Year introduced: 1991(1979)
    MeSH
  • Nuclear Pore
    Nuclear Pore
    An opening through the NUCLEAR ENVELOPE formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the CELL NUCLEUS and which, under some condi...<br/>Year introduced: 2001
    MeSH
  • Cerebrosides
    Cerebrosides
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    MeSH

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001218184Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 24, 2020) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV001218184.4

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TYK2-related conditions. This variant is present in population databases (rs557436288, ExAC 0.004%). This sequence change replaces arginine with cysteine at codon 220 of the TYK2 protein (p.Arg220Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine.

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

Last Updated: Sep 29, 2024