Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002026626 | SCV002308055 | uncertain significance | Growth hormone insensitivity with immune dysregulation 1, autosomal recessive | 2021-12-23 | criteria provided, single submitter | clinical testing | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with STAT5B-related conditions. This variant is present in population databases (rs750520285, gnomAD 0.002%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 66 of the STAT5B protein (p.Gln66Arg). |
| St. |
RCV002026626 | SCV004171396 | uncertain significance | Growth hormone insensitivity with immune dysregulation 1, autosomal recessive | 2023-11-06 | criteria provided, single submitter | clinical testing | The STAT5B c.197A>G (p.Gln66Arg) missense change has a maximum subpopulation frequency of 0.0018% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in the literature in individuals with STAT5B-associated clinical phenotypes. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |