Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001054094 | SCV001218389 | uncertain significance | Juvenile polyposis syndrome | 2023-09-30 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 182 of the SMAD4 protein (p.Ile182Val). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SMAD4 protein function. ClinVar contains an entry for this variant (Variation ID: 850013). This variant has not been reported in the literature in individuals affected with SMAD4-related conditions. This variant is not present in population databases (gnomAD no frequency). |
Sema4, |
RCV002258110 | SCV002538331 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-03 | criteria provided, single submitter | curation | |
All of Us Research Program, |
RCV004000066 | SCV004818577 | uncertain significance | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome | 2023-02-24 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 182 of the SMAD4 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SMAD4-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |