Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002385159 | SCV002694608 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-08-21 | criteria provided, single submitter | clinical testing | The p.C318Y variant (also known as c.953G>A), located in coding exon 3 of the BLM gene, results from a G to A substitution at nucleotide position 953. The cysteine at codon 318 is replaced by tyrosine, 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003505246 | SCV004279819 | uncertain significance | Bloom syndrome | 2023-04-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1767312). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 318 of the BLM protein (p.Cys318Tyr). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BLM 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. |