Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001233520 | SCV001406120 | uncertain significance | Bloom syndrome | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with threonine at codon 48 of the BLM protein (p.Ser48Thr). The serine residue is weakly conserved and there is a small physicochemical difference between serine and threonine. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV003284091 | SCV004003083 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-03 | criteria provided, single submitter | clinical testing | The p.S48T variant (also known as c.142T>A), located in coding exon 2 of the BLM gene, results from a T to A substitution at nucleotide position 142. The serine at codon 48 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |