Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000160963 | SCV000211672 | pathogenic | not provided | 2014-09-17 | criteria provided, single submitter | clinical testing | This pathogenic variant is denoted SMAD4 c.1239C>A at the cDNA level and p.Tyr413Ter (Y413X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAC>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this specific variant has not, to our knowledge, been reported in the literature, a different nucleotide substitution leading to the same truncating variant has been published in a Juvenile Polyposis Syndrome family (Jee 2013). We consider SMAD4 Tyr413Ter to be pathogenic. |
Invitae | RCV001850275 | SCV002227805 | pathogenic | Juvenile polyposis syndrome | 2021-09-21 | 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: 182871). This premature translational stop signal has been observed in individual(s) with clinical features of juvenile polyposis syndrome (PMID: 24312718, 26681312). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr413*) 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). |