ClinVar Miner

Submissions for variant NM_001083962.2(TCF4):c.1420del (p.Val474fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center RCV004784995 SCV005397346 likely pathogenic Pitt-Hopkins syndrome 2023-07-06 criteria provided, single submitter clinical testing This sequence variant is a single nucleotide deletion (delC) in exon 16 of 20 of the TCF4 gene and results in an early termition sigl 14 amino acids downstream of the frameshift introduced at codon 474. This variant is predicted to generate a non-functiol allele through either the expression of a truncated protein or a loss of TCF4-expression due to nonsense mediated decay. This variant is absent from ClinVar and the gnomAD population database (0 of approximately 250,000 alleles). To our knowledge, this variant has not been observed in an individual affected by a TCF4-related disorder in the published literature and studies examining the functiol consequence of this variant have not been published. Nonetheless haploinsufficiency in TCF4 is a known mechanism of disease (PMID: 22934316). Based upon the evidence, we consider this a likely pathogenic variant. ACMG Criteria: PM2, PVS1

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