Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001928971 | SCV002200282 | uncertain significance | Bloom syndrome | 2021-06-20 | criteria provided, single submitter | clinical testing | 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 alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with BLM-related conditions. This sequence change replaces threonine with alanine at codon 1385 of the BLM protein (p.Thr1385Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002331463 | SCV002629431 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-02 | criteria provided, single submitter | clinical testing | The p.T1385A variant (also known as c.4153A>G), located in coding exon 21 of the BLM gene, results from an A to G substitution at nucleotide position 4153. The threonine at codon 1385 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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. |