Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000820182 | SCV000960883 | uncertain significance | Bloom syndrome | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 972 of the BLM protein (p.Gly972Val). This variant is present in population databases (rs150475674, 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: 662521). 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 expected to disrupt BLM protein function. Experimental studies have shown that this missense change affects BLM function (PMID: 23129629, 26788541). 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 | RCV001016923 | SCV001177930 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-23 | criteria provided, single submitter | clinical testing | The p.G972V variant (also known as c.2915G>T), located in coding exon 14 of the BLM gene, results from a G to T substitution at nucleotide position 2915. The glycine at codon 972 is replaced by valine, an amino acid with dissimilar properties. Functional studies performed in yeast showed increased sensitivity to DNA damaging agents comparable to that of known BLM mutations (Mirzaei H et al. Proc. Natl. Acad. Sci. U.S.A. 2012 Nov;109:19357-62; Shastri VM et al. Mol Genet Genomic Med. 2016 Jan;4:106-19). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV000820182 | SCV001454867 | uncertain significance | Bloom syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |