Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001056148 | SCV001220570 | uncertain significance | Growth hormone insensitivity with immune dysregulation 1, autosomal recessive | 2023-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 180 of the STAT5B protein (p.Leu180Gln). 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. ClinVar contains an entry for this variant (Variation ID: 851703). 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. 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 | RCV002554395 | SCV003677919 | uncertain significance | Inborn genetic diseases | 2022-12-28 | criteria provided, single submitter | clinical testing | The c.539T>A (p.L180Q) alteration is located in exon 5 (coding exon 4) of the STAT5B gene. This alteration results from a T to A substitution at nucleotide position 539, causing the leucine (L) at amino acid position 180 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Clinical Genomics Laboratory, |
RCV003458609 | SCV004177143 | uncertain significance | Growth hormone insensitivity syndrome with immune dysregulation | 2023-07-26 | criteria provided, single submitter | clinical testing | The STAT5B c.539T>A (p.Leu180Gln) variant, to our knowledge, has not been reported in the medical literature but has been reported in the ClinVar database as a germline variant of uncertain significance by two submitters. This variant is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. The amino acid at this position occurs in the coiled-coil domain at the end of one of the coils and the variant replaces the non-polar leucine with a polar glutamine (AlphaFold; Maurer B et al., PMID: 31690038). Additionally, a nearby missense variant, p.Gln177Pro, has been described as occurring de novo in a set of affected twins and the variant abrogated nuclear import, thus acting as a dominant negative (Klammt J et al., PMID: 29844444). However, computational predictors are uncertain as to the impact of this variant on STAT5B function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time. |