ClinVar Miner

Submissions for variant NM_001083962.2(TCF4):c.1469C>G (p.Pro490Arg)

dbSNP: rs1555722023
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000535942 SCV000646111 likely pathogenic Pitt-Hopkins syndrome 2020-03-05 criteria provided, single submitter clinical testing In summary, this variant is a novel de novo missense change observed in an affected individual which suggests it is pathogenic, however, in the absence of functional data, it has been classified as Likely Pathogenic.. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Family studies indicate this variant likely was not inherited from either parent (i.e. occurred de novo) in an individual with disease (Invitae database). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TCF4-related disease. This sequence change replaces proline with arginine at codon 490 of the TCF4 protein (p.Pro490Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine.

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