Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000534140 | SCV000623343 | uncertain significance | Bloom syndrome | 2022-02-11 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 208 of the BLM protein (p.Leu208Trp). This variant is not present in population databases (gnomAD no frequency). 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: 454159). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 | RCV002367760 | SCV002656403 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-04-24 | criteria provided, single submitter | clinical testing | The p.L208W variant (also known as c.623T>G), located in coding exon 2 of the BLM gene, results from a T to G substitution at nucleotide position 623. The leucine at codon 208 is replaced by tryptophan, 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. |