ClinVar Miner

Submissions for variant NM_003331.5(TYK2):c.209_212del (p.Cys70fs)

dbSNP: rs770927552
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center RCV000014228 SCV000267549 pathogenic Immunodeficiency 35 2016-03-18 criteria provided, single submitter reference population
GeneDx RCV000519417 SCV000617554 pathogenic not provided 2017-10-30 criteria provided, single submitter clinical testing The c.209_212delGCTT variant in the TYK2 gene has been reported previously in the homozygous state in an individual with hyper-IgE syndrome (Minegishi et al., 2006). The c.209_212delGCTT variant causes a frameshift starting with codon Cysteine 70, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 21 of the new reading frame, denoted p.Cys70SerfsX21. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.209_212delGCTT variant is observed in 12/17248 (0.07%) alleles, although not in the homozygous state, from individuals of East Asian background, in large population cohorts (Lek et al., 2016). We interpret c.209_212delGCTT as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000014228 SCV003442657 pathogenic Immunodeficiency 35 2023-11-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys70Serfs*21) 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). This variant is present in population databases (rs770927552, gnomAD 0.07%). This premature translational stop signal has been observed in individual(s) with mendelian susceptibility to mycobacterial disease (PMID: 29725107). ClinVar contains an entry for this variant (Variation ID: 225508). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000014228 SCV000034476 pathogenic Immunodeficiency 35 2006-11-01 no assertion criteria provided literature only

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