Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002233988 | SCV000756870 | uncertain significance | Juvenile polyposis syndrome | 2022-08-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln549*) in the SMAD4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 4 amino acid(s) of the SMAD4 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMAD4-related conditions. ClinVar contains an entry for this variant (Variation ID: 529928). 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. |
| Ambry Genetics | RCV002388034 | SCV002703780 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome | 2020-03-25 | criteria provided, single submitter | clinical testing | The p.Q549* variant (also known as c.1645C>T), located in coding exon 11 of the SMAD4 gene, results from a C to T substitution at nucleotide position 1645. This changes the amino acid from a glutamine to a stop codon within coding exon 11. Premature stop codons are typically deleterious in nature; however, this stop codon occurs at the 3' terminus of SMAD4, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last four amino acids of the protein. The exact functional impact of these removed amino acids is unknown at this time. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |