ClinVar Miner

Submissions for variant NM_001083962.2(TCF4):c.1965dup (p.Gly656fs)

dbSNP: rs797046035
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel 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, University of Chicago RCV000192539 SCV000249131 likely pathogenic Pitt-Hopkins syndrome 2015-06-03 criteria provided, single submitter clinical testing
UCLA Clinical Genomics Center, UCLA RCV000192539 SCV000255487 pathogenic Pitt-Hopkins syndrome 2014-06-10 criteria provided, single submitter clinical testing

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