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

Clear Turn Off Turn On

Psathyrella gordonii voucher LO220-95 internal transcribed spacer 1, partial seq...
Psathyrella gordonii voucher LO220-95 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene and internal transcribed spacer 2, complete sequence; and large subunit ribosomal RNA gene, partial sequence
gi|557116266|gb|KC992924.1|

Nucleotide
Plasma Substitutes [Pharmacological Action]
Plasma Substitutes [Pharmacological Action]

MeSH
Psychosine
Psychosine
An intermediate in the biosynthesis of cerebrosides. It is formed by reaction of sphingosine with UDP-galactose and then itself reacts with fatty acid-Coenzyme A to form the c...<br/>Year introduced: 1991(1975)

MeSH

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001218184	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 24, 2020)	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

SCV001218184

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 24, 2020)

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, SCV001218184.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	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

ClinVar

Relating variation to medicine