Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001340298 | SCV001534099 | uncertain significance | Growth hormone insensitivity with immune dysregulation 1, autosomal recessive | 2020-07-29 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with STAT5B-related conditions. This variant is present in population databases (rs547016204, ExAC 0.02%). This sequence change replaces serine with proline at codon 787 of the STAT5B protein (p.Ser787Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. |
Neuberg Centre For Genomic Medicine, |
RCV004546637 | SCV005042574 | uncertain significance | Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant | criteria provided, single submitter | clinical testing | The missense c.2359T>Cp.Ser787Pro variant in STAT5B gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Ser787Pro variant has been reported with allele frequency of 0.002% in gnomAD Exomes and is novel not in any individuals in 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Ser787Pro in STAT5B is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Ser at position 787 is changed to a Pro changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance VUS. |