ClinVar Miner

Submissions for variant NM_001083962.2(TCF4):c.650T>C (p.Met217Thr)

dbSNP: rs2146263735
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001754361 SCV001987465 uncertain significance not provided 2019-05-23 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001882812 SCV002114967 uncertain significance Pitt-Hopkins syndrome 2022-10-17 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. ClinVar contains an entry for this variant (Variation ID: 1302472). 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 replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 217 of the TCF4 protein (p.Met217Thr).

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