Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000523517 | SCV000618772 | uncertain significance | not provided | 2017-07-06 | criteria provided, single submitter | clinical testing | The I332T variant in the SMAD2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I332T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I332T 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. We interpret I332T as a variant of uncertain significance. |
| Labcorp Genetics |
RCV000523517 | SCV004485407 | uncertain significance | not provided | 2024-11-11 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 332 of the SMAD2 protein (p.Ile332Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMAD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 450219). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |