Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000703064 | SCV000831945 | uncertain significance | Bloom syndrome | 2024-08-07 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 623 of the BLM protein (p.Ile623Thr). 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: 579713). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The threonine 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. |
Gene |
RCV001766546 | SCV002000648 | uncertain significance | not provided | 2021-04-28 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002406636 | SCV002721044 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-04 | criteria provided, single submitter | clinical testing | The p.I623T variant (also known as c.1868T>C), located in coding exon 6 of the BLM gene, results from a T to C substitution at nucleotide position 1868. The isoleucine at codon 623 is replaced by threonine, 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. |
Natera, |
RCV000703064 | SCV002092405 | uncertain significance | Bloom syndrome | 2020-02-26 | no assertion criteria provided | clinical testing |