Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001241217 | SCV001414222 | uncertain significance | Bloom syndrome | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with phenylalanine at codon 393 of the BLM protein (p.Leu393Phe). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BLM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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 | RCV002327583 | SCV002635405 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-04 | criteria provided, single submitter | clinical testing | The p.L393F variant (also known as c.1177C>T), located in coding exon 5 of the BLM gene, results from a C to T substitution at nucleotide position 1177. The leucine at codon 393 is replaced by phenylalanine, 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. |