Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002513159 | SCV000833066 | pathogenic | Juvenile polyposis syndrome | 2022-10-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 24813). This variant is also known as 729-730insCCGC. This premature translational stop signal has been observed in individual(s) with juvenile polyposis syndrome (PMID: 16436638). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln245Profs*20) in the SMAD4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMAD4 are known to be pathogenic (PMID: 16152648, 16436638, 22810475). |
| Ambry Genetics | RCV002381259 | SCV002668440 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome | 2020-09-17 | criteria provided, single submitter | clinical testing | The c.731_732insGCCC pathogenic mutation, located in coding exon 5 of the SMAD4 gene, results from an insertion of 4 nucleotides at position 731, causing a translational frameshift with a predicted alternate stop codon (p.Q245Pfs*20). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Myriad Genetics, |
RCV003450650 | SCV004185997 | pathogenic | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome | 2023-11-06 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |