Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002442217 | SCV002746291 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-09-30 | criteria provided, single submitter | clinical testing | The c.2981_2982delCCinsAG variant (also known as p.T994K), located in coding exon 14 of the BLM gene, results from a deletion of CC and insertion of AG at nucleotide positions 2981 to 2982. The threonine at codon 994 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV005098368 | SCV005778892 | uncertain significance | Bloom syndrome | 2024-05-16 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 994 of the BLM protein (p.Thr994Lys). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 1798403). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |