ClinVar Miner

Submissions for variant NM_001083962.2(TCF4):c.1876C>T (p.Arg626Ter) (rs1131691735)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493014 SCV000582727 pathogenic not provided 2018-08-27 criteria provided, single submitter clinical testing The R626X nonsense variant in the TCF4 gene has been reported previously in three individuals with Pitt-Hopkins syndrome (Whalen et al., 2012). This pathogenic variant is predicted to cause loss of normal protein function through protein truncation. The R626X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R626X as a pathogenic variant.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000660298 SCV000782335 likely pathogenic Pitt-Hopkins syndrome 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000660298 SCV000819174 pathogenic Pitt-Hopkins syndrome 2018-05-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg626*) in the TCF4 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals affected with Pitt–Hopkins Syndrome (PMID: 22045651). ClinVar contains an entry for this variant (Variation ID: 430016). Loss-of-function variants in TCF4 are known to be pathogenic (PMID: 18728071, 22045651). For these reasons, this variant has been classified as Pathogenic.

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