Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000706704 | SCV000835771 | uncertain significance | Bloom syndrome | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with serine at codon 728 of the BLM protein (p.Thr728Ser). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BLM-related conditions. 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: "Possibly 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. |
Ambry Genetics | RCV003353000 | SCV004076450 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-23 | criteria provided, single submitter | clinical testing | The p.T728S variant (also known as c.2183C>G), located in coding exon 8 of the BLM gene, results from a C to G substitution at nucleotide position 2183. The threonine at codon 728 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV000706704 | SCV002088037 | uncertain significance | Bloom syndrome | 2020-07-24 | no assertion criteria provided | clinical testing |