ClinVar Miner

Submissions for variant NM_003331.5(TYK2):c.437C>T (p.Pro146Leu)

gnomAD frequency: 0.00003  dbSNP: rs137904701
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000802854 SCV000942700 uncertain significance Immunodeficiency 35 2022-02-14 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 146 of the TYK2 protein (p.Pro146Leu). This variant is present in population databases (rs137904701, gnomAD 0.004%). 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: 648186). 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.
PreventionGenetics, part of Exact Sciences RCV003413607 SCV004108888 uncertain significance TYK2-related disorder 2022-11-07 criteria provided, single submitter clinical testing The TYK2 c.437C>T variant is predicted to result in the amino acid substitution p.Pro146Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0035% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-10478759-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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