Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001361204 | SCV001557170 | uncertain significance | Bloom syndrome | 2020-08-04 | 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: "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. This variant has not been reported in the literature in individuals with BLM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 777 of the BLM protein (p.Ile777Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine. |
| Ambry Genetics | RCV004601475 | SCV005101877 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-07 | criteria provided, single submitter | clinical testing | The p.I777T variant (also known as c.2330T>C), located in coding exon 10 of the BLM gene, results from a T to C substitution at nucleotide position 2330. The isoleucine at codon 777 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |