Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000776864 | SCV000912528 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-30 | criteria provided, single submitter | clinical testing | |
NIHR Bioresource Rare Diseases, |
RCV001262036 | SCV001439413 | likely pathogenic | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome | 2018-01-01 | criteria provided, single submitter | research | PM2+PM1+PP3+PP4 |
Labcorp Genetics |
RCV001856136 | SCV002199587 | uncertain significance | Juvenile polyposis syndrome | 2021-11-15 | 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 630855). This missense change has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (PMID: 32573726). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 437 of the SMAD4 protein (p.Val437Ile). |
Baylor Genetics | RCV001262036 | SCV004202587 | uncertain significance | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome | 2023-08-09 | criteria provided, single submitter | clinical testing |