Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000705545 | SCV000834546 | uncertain significance | Bloom syndrome | 2023-04-06 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 581653). This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1007 of the BLM protein (p.Met1007Ile). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002265866 | SCV002548388 | uncertain significance | not specified | 2022-05-12 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002440537 | SCV002753081 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-03 | criteria provided, single submitter | clinical testing | The p.M1007I variant (also known as c.3021G>A), located in coding exon 15 of the BLM gene, results from a G to A substitution at nucleotide position 3021. The methionine at codon 1007 is replaced by isoleucine, an amino acid with highly similar 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. |