Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001316235 | SCV001506842 | uncertain significance | Bloom syndrome | 2020-11-03 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine 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. This variant has not been reported in the literature in individuals with BLM-related conditions. This variant is present in population databases (rs144021705, ExAC 0.002%). This sequence change replaces threonine with isoleucine at codon 1074 of the BLM protein (p.Thr1074Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. |