Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001220307 | SCV001392287 | uncertain significance | Bloom syndrome | 2022-07-08 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1124 of the BLM protein (p.Ala1124Val). 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 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 948949). This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is present in population databases (rs751765688, gnomAD 0.0009%). |
Ambry Genetics | RCV002451504 | SCV002615537 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-16 | criteria provided, single submitter | clinical testing | The p.A1124V variant (also known as c.3371C>T), located in coding exon 17 of the BLM gene, results from a C to T substitution at nucleotide position 3371. The alanine at codon 1124 is replaced by valine, an amino acid with similar properties. This amino acid position is highly 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. |
Prevention |
RCV003898211 | SCV004715996 | uncertain significance | BLM-related condition | 2024-01-19 | criteria provided, single submitter | clinical testing | The BLM c.3371C>T variant is predicted to result in the amino acid substitution p.Ala1124Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Natera, |
RCV001220307 | SCV002090560 | uncertain significance | Bloom syndrome | 2020-03-13 | no assertion criteria provided | clinical testing |