Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002323902 | SCV002609543 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-17 | criteria provided, single submitter | clinical testing | The c.1132_1134delCACinsTAT variant, located in coding exon 5 of the BLM gene, results from an in-frame deletion of CAC and insertion of TAT at nucleotide positions 1132 to 1134. This results in the substitution of the histidine residue for a tyrosine residue at codon 378, 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 neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV000548596 | SCV002778588 | uncertain significance | Bloom syndrome | 2022-01-17 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000548596 | SCV004507296 | uncertain significance | Bloom syndrome | 2021-02-02 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BLM-related disease. This variant is reported as two separate single-nucleotide changes in population databases (c.1132C>T, ExAC 0.01% and c.1134C>T, ExAC 0.01%). However, in the read data for the 2 individuals displayed in the ExAC browser, these two variants are in cis. This recapitulates the variant observed here (c.1132_1134delinsTAT) and indicates that this variant is very likely present in the population databases at 0.01%. This sequence change replaces histidine with tyrosine at codon 378 of the BLM protein (p.His378Tyr). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and tyrosine. |