Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000192539 | SCV001711977 | pathogenic | Pitt-Hopkins syndrome | 2021-03-26 | reviewed by expert panel | curation | The p.Gly656Argfs*55 variant in TCF4 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The p.Gly656Argfs*55 variant in TCF4 has been reported as a de novo occurrence (biological parentage confirmed) in an individual with Pitt-Hopkins syndrome (PMID 25326637) (PS2). This variant is absent from gnomAD (PM2_supporting). In summary, the p.Gly656Argfs*55 variant in TCF4 is classified as Pathogenic for Pitt-Hopkins syndrome based on the ACMG/AMP criteria (PVS1, PS2, PM2_supporting). |
Genetic Services Laboratory, |
RCV000192539 | SCV000249131 | likely pathogenic | Pitt-Hopkins syndrome | 2015-06-03 | criteria provided, single submitter | clinical testing | |
UCLA Clinical Genomics Center, |
RCV000192539 | SCV000255487 | pathogenic | Pitt-Hopkins syndrome | 2014-06-10 | criteria provided, single submitter | clinical testing |