Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012455 | SCV001172908 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-30 | criteria provided, single submitter | clinical testing | The p.I540K variant (also known as c.1619T>A), located in coding exon 6 of the BLM gene, results from a T to A substitution at nucleotide position 1619. The isoleucine at codon 540 is replaced by lysine, an amino acid with dissimilar properties. This amino acid position is poorly 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. |
| Invitae | RCV001315005 | SCV001505559 | uncertain significance | Bloom syndrome | 2020-10-10 | 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 tolerated, 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. ClinVar contains an entry for this variant (Variation ID: 819684). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with lysine at codon 540 of the BLM protein (p.Ile540Lys). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and lysine. |