Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001049643 | SCV001213708 | uncertain significance | Bloom syndrome | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 591 of the BLM protein (p.Arg591Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD 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: 846355). 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: "Deleterious"; PolyPhen-2: "Benign"; 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 | RCV002409425 | SCV002716851 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-07 | criteria provided, single submitter | clinical testing | The p.R591W variant (also known as c.1771C>T), located in coding exon 6 of the BLM gene, results from a C to T substitution at nucleotide position 1771. The arginine at codon 591 is replaced by tryptophan, an amino acid with dissimilar properties. 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. |
Natera, |
RCV001049643 | SCV002092393 | uncertain significance | Bloom syndrome | 2019-02-02 | no assertion criteria provided | clinical testing |