Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001010706 | SCV001170939 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-16 | criteria provided, single submitter | clinical testing | The p.S426L variant (also known as c.1277C>T), located in coding exon 6 of the BLM gene, results from a C to T substitution at nucleotide position 1277. The serine at codon 426 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well 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. |
Labcorp Genetics |
RCV001058441 | SCV001223014 | uncertain significance | Bloom syndrome | 2022-02-11 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 426 of the BLM protein (p.Ser426Leu). This variant is present in population databases (rs768127491, 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: 818776). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine 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. |
Fulgent Genetics, |
RCV001058441 | SCV002803841 | uncertain significance | Bloom syndrome | 2022-05-16 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001058441 | SCV002090024 | uncertain significance | Bloom syndrome | 2018-08-16 | no assertion criteria provided | clinical testing |