Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000490089 | SCV000577793 | likely pathogenic | not provided | 2015-05-11 | criteria provided, single submitter | clinical testing | The p.Cys376Ser variant in the LAMB3 gene has not been reported previously as a disease-causing variant nor as a benign polymorphism, to our knowledge. The p.Cys376Ser variant 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. The p.Cys376Ser variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Since Cysteines are often involved in disulfide bonding and are important for protein secondary structure and for associations between proteins. Missense variant in nearby residues (R366W) have been reported in the Human Gene Mutation Database in association with JEB (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret p.Cys376Ser as a disease-causing variant |