Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000147722 | SCV000195187 | pathogenic | Pitt-Hopkins syndrome | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Seattle Children's Hospital Molecular Genetics Laboratory, |
RCV000147722 | SCV005326322 | likely pathogenic | Pitt-Hopkins syndrome | criteria provided, single submitter | clinical testing | The p.Leu139Phefs*95 variant substitutes the leucine at amino acid position 139 with phenylalanine followed by a premature stop codon after 95 residues. This is predicted to result in loss-of-function of the TCF4 protein. While the p.Leu139Phefs*95 variant has not been reported in the medical literature, loss-of-function of TCF4 is a known disease mechanism for Pitt-Hopkins syndrome (MIM: 610954) (PMID: 34837432). The p.Leu139Phefs*95 variant is reported in a patient database in an individual with Pitt-Hopkins syndrome (ClinVar Variation ID: 160084). The p.Leu139Phefs*95 variant is absent from large population studies (gnomAD v2.1.1). |