Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000529683 | SCV000623294 | uncertain significance | Bloom syndrome | 2024-09-28 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 987 of the BLM protein (p.Ser987Phe). 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: 454123). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt BLM protein function with a positive predictive value of 80%. 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 | RCV003159710 | SCV003892190 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-14 | criteria provided, single submitter | clinical testing | The p.S987F variant (also known as c.2960C>T), located in coding exon 14 of the BLM gene, results from a C to T substitution at nucleotide position 2960. The serine at codon 987 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |