Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010093 | SCV001170241 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-29 | criteria provided, single submitter | clinical testing | The p.K390T variant (also known as c.1169A>C), located in coding exon 5 of the BLM gene, results from an A to C substitution at nucleotide position 1169. The lysine at codon 390 is replaced by threonine, an amino acid with similar 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 | RCV002550756 | SCV003297841 | uncertain significance | Bloom syndrome | 2022-01-14 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 390 of the BLM protein (p.Lys390Thr). This variant has not been reported in the literature in individuals affected with BLM-related conditions. 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. ClinVar contains an entry for this variant (Variation ID: 818477). |