ClinVar

Description

c.483delC: p.Glu162LysfsX24 in exon 3 in the SMAD3 gene (NM_005902.3). The normal sequence with the base that is deleted in braces is: TCCC{C}GAAA. The c.483delC mutation in the SMAD3 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. The c.483delC mutation causes a frameshift starting with codon Glutamic acid 162, changes this amino acid to a Lysine residue and creates a premature Stop codon at position 24 of the new reading frame, denoted p.Glu162LysfsX24. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.483delC mutation was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Other frameshift mutations in the SMAD3 gene have been reported in association with Loeys-Dietz syndrome type 3. We interpret c.483delC as a disease-causing mutation. This variant has been observed to be maternally inherited. This variant was found in SMAD3