ClinVar Miner

Submissions for variant NM_001083962.2(TCF4):c.1165C>T (p.Arg389Cys)

dbSNP: rs2145503179
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001822000 SCV002011164 likely pathogenic not provided 2021-11-03 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001822000 SCV002072098 likely pathogenic not provided 2017-11-09 criteria provided, single submitter clinical testing
Invitae RCV001769978 SCV002130656 pathogenic Pitt-Hopkins syndrome 2023-08-31 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 389 of the TCF4 protein (p.Arg389Cys). This missense change has been observed in individual(s) with neurological disorder and/or Pitt-Hopkins syndrome (PMID: 34490615, 35908153). In at least one individual the variant was observed to be de novo. This variant is also known as c.1471C>T, p.(Arg491Cys). ClinVar contains an entry for this variant (Variation ID: 1319340). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TCF4 protein function. For these reasons, this variant has been classified as Pathogenic.
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV001769978 SCV004013192 pathogenic Pitt-Hopkins syndrome 2023-05-10 criteria provided, single submitter clinical testing PS2_Very Strong, PS4, PM2, PP2, PP3
DECIPHERD-UDD, Universidad del Desarrollo RCV001769978 SCV004170977 likely pathogenic Pitt-Hopkins syndrome 2023-07-01 criteria provided, single submitter research

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