Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000798525 | SCV000938145 | uncertain significance | Bloom syndrome | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 188 of the BLM protein (p.Lys188Arg). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 644576). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 | RCV002345774 | SCV002652880 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-19 | criteria provided, single submitter | clinical testing | The p.K188R variant (also known as c.563A>G), located in coding exon 2 of the BLM gene, results from an A to G substitution at nucleotide position 563. The lysine at codon 188 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. 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, |
RCV000798525 | SCV002089947 | uncertain significance | Bloom syndrome | 2018-08-09 | no assertion criteria provided | clinical testing | |
Prevention |
RCV003947988 | SCV004763397 | uncertain significance | BLM-related disorder | 2023-11-20 | no assertion criteria provided | clinical testing | The BLM c.563A>G variant is predicted to result in the amino acid substitution p.Lys188Arg. To our knowledge, this variant has not been reported in the literature. This variant has been reported as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/644576/). This variant is reported in 0.00092% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-91293061-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |