ClinVar Miner

Submissions for variant NM_003331.5(TYK2):c.1342C>T (p.Arg448Trp)

gnomAD frequency: 0.00008  dbSNP: rs147991080
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000704140 SCV000833078 uncertain significance Immunodeficiency 35 2022-08-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 448 of the TYK2 protein (p.Arg448Trp). This variant is present in population databases (rs147991080, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TYK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 580559). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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.
Illumina Laboratory Services, Illumina RCV000704140 SCV001282483 uncertain significance Immunodeficiency 35 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Baylor Genetics RCV000704140 SCV001522962 uncertain significance Immunodeficiency 35 2020-04-27 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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