Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV001449801 | SCV001653087 | likely pathogenic | Familial aplasia of the vermis | 2020-07-07 | criteria provided, single submitter | clinical testing | The p.Leu663AlafsX35 variant in CPLANE1 (previously called C5orf42) has not been previously reported in individuals with Joubert syndrome and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 663 and leads to a premature termination codon 34 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the CPLANE1 gene is an established disease mechanism in autosomal recessive Joubert syndrome. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Joubert syndrome. ACMG/AMP Criteria applied: PVS1, PM2. |