Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001914720 | SCV002145635 | uncertain significance | Bloom syndrome | 2021-05-04 | criteria provided, single submitter | clinical testing | 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. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 tyrosine with asparagine at codon 1160 of the BLM protein (p.Tyr1160Asn). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and asparagine. |
| Ambry Genetics | RCV004041144 | SCV005023380 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-25 | criteria provided, single submitter | clinical testing | The p.Y1160N variant (also known as c.3478T>A), located in coding exon 17 of the BLM gene, results from a T to A substitution at nucleotide position 3478. The tyrosine at codon 1160 is replaced by asparagine, an amino acid with dissimilar 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. |