Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000798828 | SCV000938461 | uncertain significance | Generalized juvenile polyposis/juvenile polyposis coli | 2018-09-05 | criteria provided, single submitter | clinical testing | This variant is a deletion of the genomic region encompassing the non-coding exon 1 of the SMAD4 gene. While deletions of exon 1 have not been reported in the literature, a deletion encompassing exon 1 and additional flanking intergenic and intronic sequences has been observed in an individual affected with juvenile polyposis (PMID: 21421563). The clinical significance of deletion of exon 1 alone is still unknown. This variant disrupts a portion of Promotor C of the SMAD4 protein, which has been shown to have significant transcriptional activity (PMID: 21421563). While functional studies have not been performed to directly test the effect of exon 1 deletions on SMAD4 protein function, the functional significance of Promoter C suggests that disruption of part or all this region of the protein may be causative of disease. 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. |
| Invitae | RCV001873239 | SCV002213883 | uncertain significance | Juvenile polyposis syndrome | 2021-08-12 | criteria provided, single submitter | clinical testing | This variant occurs in a non-coding region of the SMAD4 gene. It does not change the encoded amino acid sequence of the SMAD4 protein. A similar copy number variant has been observed in individuals with clinical features of SMAD4-related conditions (PMID: 21421563; Invitae). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that a similar copy number variant affects SMAD4 function (PMID: 21421563). 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. |