Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000815041 | SCV000955482 | uncertain significance | Bloom syndrome | 2023-12-10 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 1393 of the BLM protein (p.Asn1393Asp). This variant is present in population databases (rs548600410, gnomAD 0.002%). 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: 658251). 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. 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 | RCV001021993 | SCV001183679 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-26 | criteria provided, single submitter | clinical testing | The p.N1393D variant (also known as c.4177A>G), located in coding exon 21 of the BLM gene, results from an A to G substitution at nucleotide position 4177. The asparagine at codon 1393 is replaced by aspartic acid, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with colorectal cancer (DeRycke MS et al. Mol Genet Genomic Med, 2017 Sep;5:553-569). 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. |
Sema4, |
RCV001021993 | SCV002533084 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-27 | criteria provided, single submitter | curation | |
Fulgent Genetics, |
RCV000815041 | SCV002791459 | uncertain significance | Bloom syndrome | 2021-07-09 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003324800 | SCV004030552 | uncertain significance | not provided | 2023-02-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28944238) |
Natera, |
RCV000815041 | SCV001461030 | uncertain significance | Bloom syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |