ClinVar Miner

Submissions for variant NM_001083962.2(TCF4):c.1705C>T (p.Arg569Trp)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV000760226 SCV000890056 pathogenic Pitt-Hopkins syndrome; Corneal dystrophy, Fuchs endothelial, 3 2017-03-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001855923 SCV002278147 likely pathogenic Pitt-Hopkins syndrome 2021-05-13 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with Pitt–Hopkins syndrome (PMID: 29695756). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 620020). This sequence change replaces arginine with tryptophan at codon 569 of the TCF4 protein (p.Arg569Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan.

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