Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002957644 | SCV003271397 | uncertain significance | Immunodeficiency 35 | 2024-11-11 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 948 of the TYK2 protein (p.Ile948Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 2060278). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TYK2 protein function with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV003274090 | SCV003985617 | uncertain significance | Inborn genetic diseases | 2023-05-24 | criteria provided, single submitter | clinical testing | The c.2843T>C (p.I948T) alteration is located in exon 20 (coding exon 18) of the TYK2 gene. This alteration results from a T to C substitution at nucleotide position 2843, causing the isoleucine (I) at amino acid position 948 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |