Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clinical Genomics Laboratory, |
RCV001253781 | SCV001427072 | pathogenic | Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 | 2019-08-16 | no assertion criteria provided | clinical testing | The p.Gln715* variant in the TBCK gene was identified in homozygous state in this individual, but has not been previously reported in association with disease. This variant leads to a premature stop codon in exon 23 of 26 coding exons, and is therefore predicted to undergo nonsense-mediated decay resulting in a truncated or absent protein. The p.Gln715* variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Gln715* variant as pathogenic for autosomal recessive TBCK-associated neurodevelopmental disorder based on the information above. [ACMG evidence codes used: PVS1, PM2, PM3_Supporting] |