Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001008248 | SCV001168014 | likely pathogenic | not provided | 2018-07-02 | criteria provided, single submitter | clinical testing | The c.399delG variant in the ATP7B gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. However, a nonsense variant at this same codon (W133X) has been reported in an individual with Wilson disease, however additional information on if a second ATP7B variant was seen in this individual was not provided (Cheng et al., 2017). The c.399delG variant causes a frameshift starting with codon Tryptophan 133, changes this amino acid to a Cysteine residue, and creates a premature Stop codon at position 20 of the new reading frame, denoted p.Trp133CysfsX20. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.399delG variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.399delG as a likely pathogenic variant. |