Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002328473 | SCV002638915 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-25 | criteria provided, single submitter | clinical testing | The p.S149N variant (also known as c.446G>A), located in coding exon 2 of the BLM gene, results from a G to A substitution at nucleotide position 446. The serine at codon 149 is replaced by asparagine, an amino acid with highly 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. |
Labcorp Genetics |
RCV003102588 | SCV003492454 | uncertain significance | Bloom syndrome | 2021-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with asparagine at codon 149 of the BLM protein (p.Ser149Asn). The serine residue is weakly conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs750929735, ExAC 0.006%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |