Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV001225255 | SCV001397513 | uncertain significance | Glanzmann thrombasthenia | 2023-10-17 | reviewed by expert panel | curation | To our knowledge, this c.1072C>T (p.Arg358Cys) variant has not been reported in the literature. It is absent from population databases, including gnomADv2.1.1 (PM2_supporting). This variant occurs at the same amino acid residue as Arg358His, a previously reported pathogenic missense change (PM5). In summary, this variant meets criteria to be classified as uncertain significance for autosomal recessive Glanzmann thrombasthenia. GT-specific criteria applied: PM2_Supporting and PM5. |
| Gene |
RCV000489864 | SCV000577176 | uncertain significance | not provided | 2017-04-07 | criteria provided, single submitter | clinical testing | The R358C variant in the ITGA2B gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R358C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R358C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue (R358H) has been reported previously in individuals with Glanzmann thrombasthenia (Nurden et al., 2011; Wilcox et al., 1995). Molecular modeling strongly suggests that the R358H variant, referred to as R327H using alternate nomenclature, acts by destabilizing the aIIbß propeller (Nurden et al., 2011). Therefore, we interpret R358C as a variant of uncertain significance. |