Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000565575 | SCV000672967 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-07 | criteria provided, single submitter | clinical testing | The p.P76S variant (also known as c.226C>T), located in coding exon 2 of the BLM gene, results from a C to T substitution at nucleotide position 226. The proline at codon 76 is replaced by serine, an amino acid with similar 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 |
RCV000628621 | SCV000749525 | uncertain significance | Bloom syndrome | 2022-10-08 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 76 of the BLM protein (p.Pro76Ser). This variant is present in population databases (rs768843912, gnomAD 0.003%). 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: 485337). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine 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. |
| Natera, |
RCV000628621 | SCV002089900 | uncertain significance | Bloom syndrome | 2020-10-28 | no assertion criteria provided | clinical testing | |
| Prevention |
RCV003900276 | SCV004715160 | uncertain significance | BLM-related disorder | 2023-12-20 | no assertion criteria provided | clinical testing | The BLM c.226C>T variant is predicted to result in the amino acid substitution p.Pro76Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD. In ClinVar, this variant is interpreted as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/485337/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |