Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000703554 | SCV000832458 | uncertain significance | Bloom syndrome | 2022-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 613 of the BLM protein (p.Thr613Ile). This variant is present in population databases (rs550417200, gnomAD 0.02%). 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: 580108). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BLM protein function. 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. |
| Ambry Genetics | RCV001013311 | SCV001173884 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-16 | criteria provided, single submitter | clinical testing | The p.T613I variant (also known as c.1838C>T), located in coding exon 6 of the BLM gene, results from a C to T substitution at nucleotide position 1838. The threonine at codon 613 is replaced by isoleucine, an amino acid with similar properties. This alteration was identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS One, 2018 Apr;13:e0194098). This amino acid position is not 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. |
| Gene |
RCV001766549 | SCV002000791 | uncertain significance | not provided | 2020-02-25 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Natera, |
RCV000703554 | SCV002092398 | uncertain significance | Bloom syndrome | 2018-09-26 | no assertion criteria provided | clinical testing |