Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000708534 | SCV000837644 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2019-07-15 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon 1 of the SMAD3 gene, which includes the initiator codon. The 5' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. The 3' boundary is likely confined to intron 1 of the SMAD3 gene. This is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with SMAD3-related disease. Loss-of-function variants in SMAD3 are known to be pathogenic (PMID: 21778426, 24804794). For these reasons, this variant has been classified as Pathogenic. |
| Labcorp Genetics |
RCV003117503 | SCV003794837 | uncertain significance | Aortic valve disease 2 | 2019-07-15 | criteria provided, single submitter | clinical testing | A gross deletion of the genomic region encompassing the full coding sequence of the SMAD6 gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals with SMAD6-related disease. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SMAD6 cause 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. |