Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001360989 | SCV001556946 | uncertain significance | Bloom syndrome | 2020-03-04 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with tyrosine at codon 449 of the BLM protein (p.Ser449Tyr). The serine residue is weakly conserved and there is a large physicochemical difference between serine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals 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: "Deleterious"; PolyPhen-2: "Benign"; 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 | RCV002384508 | SCV002692390 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-20 | criteria provided, single submitter | clinical testing | The p.S449Y variant (also known as c.1346C>A), located in coding exon 6 of the BLM gene, results from a C to A substitution at nucleotide position 1346. The serine at codon 449 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is conserved. 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, |
RCV001360989 | SCV002090031 | uncertain significance | Bloom syndrome | 2020-05-14 | no assertion criteria provided | clinical testing |