Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001343173 | SCV001537137 | uncertain significance | Growth hormone insensitivity with immune dysregulation 1, autosomal recessive | 2021-06-24 | criteria provided, single submitter | clinical testing | 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. This variant has not been reported in the literature in individuals with STAT5B-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces alanine with glycine at codon 213 of the STAT5B protein (p.Ala213Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine. |
Illumina Laboratory Services, |
RCV001796452 | SCV002034808 | uncertain significance | Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant | 2021-07-14 | criteria provided, single submitter | clinical testing | The STAT5B c.638C>G (p.Ala213Gly) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The p.Ala213Gly variant is reported at a frequency of 0.000018 in the European (non-Finnish) population of the Genome Aggregation Database version 2.1.1, though this is based on two alleles in a region of good sequence coverage so the variant is presumed to be rare. Based on the limited evidence, the p.Ala213Gly variant is classified as a variant of uncertain significance for STAT5B-related growth hormone insensitivity syndrome. |