Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003857067 | SCV004660188 | uncertain significance | Growth hormone insensitivity with immune dysregulation 1, autosomal recessive | 2023-11-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 146 of the STAT5B protein (p.Gln146Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with STAT5B-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt STAT5B 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004527012 | SCV005039049 | uncertain significance | not specified | 2024-03-26 | criteria provided, single submitter | clinical testing | Variant summary: STAT5B c.436C>G (p.Gln146Glu) results in a conservative amino acid change located in the STAT transcription factor, all-alpha domain (IPR013800) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251480 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.436C>G in individuals affected with Growth Hormone Insensitivity Syndrome With Immune Dysregulation 2, Autosomal Dominant and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2998404). Based on the evidence outlined above, the variant was classified as uncertain significance. |