ClinVar Miner

Submissions for variant NM_001083962.2(TCF4):c.652C>T (p.Gln218Ter)

dbSNP: rs1064796853
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486556 SCV000573982 pathogenic not provided 2017-03-13 criteria provided, single submitter clinical testing The Q218X variant in the TCF4 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q218X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret Q218X as a pathogenic variant.
Genetic Services Laboratory, University of Chicago RCV000486556 SCV002064409 pathogenic not provided 2018-12-05 criteria provided, single submitter clinical testing DNA sequence analysis of the TCF4 gene demonstrated a sequence change, c.652C>T, which results in the creation of a premature stop codon at amino acid position, p.Gln218*. This pathogenic sequence change is predicted to result in an abnormal transcript, which is likely to be degraded. This sequence change does not appear to have been previously described in patients with TCF4-related disorder and has also not been described as a known benign sequence change in the TCF4 gene. We classify the above variant as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003507281 SCV004248438 pathogenic Pitt-Hopkins syndrome 2023-06-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 424196). This variant has not been reported in the literature in individuals affected with TCF4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln218*) in the TCF4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TCF4 are known to be pathogenic (PMID: 18728071, 22045651).

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