Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002235130 | SCV000960805 | uncertain significance | Juvenile polyposis syndrome | 2022-11-12 | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 662465). 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). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 448 of the SMAD4 protein (p.Gln448Glu). |
Ambry Genetics | RCV002318895 | SCV001171235 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome | 2021-07-08 | criteria provided, single submitter | clinical testing | The p.Q448E variant (also known as c.1342C>G), located in coding exon 10 of the SMAD4 gene, results from a C to G substitution at nucleotide position 1342. The glutamine at codon 448 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |