Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000390060 | SCV000330098 | pathogenic | not provided | 2015-12-27 | criteria provided, single submitter | clinical testing | The c.3342delCinsAAG pathogenic variant in the EHMT1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.3342delCinsAAG variant causes a frameshift starting with codon Asparagine 1114, changes this amino acid to a Lysine residue, and creates a premature Stop codon at position 47 of the new reading frame, denoted p.Asn1114LysfsX47. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.3342delCinsAAG 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. A protein truncating pathogenic variant downstream of this variant has been reported in the Human Gene Mutation Database in association with EHMT1-related disorders (Stenson et al., 2014), supporting the pathogenicity of more upstream truncating variants. We interpret c.3342delCinsAAG as a pathogenic variant. |