Submissions for variant NM_001083962.2(TCF4):c.504A>G (p.Val168=)

gnomAD frequency: 0.00037  dbSNP: rs370160994

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV001082033	SCV002540699	benign	Pitt-Hopkins syndrome	2022-02-18	reviewed by expert panel	curation	The allele frequency of the p.Val168= variant in TCF4 is 0.057% in European (Non-Finnish) sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). The p.Val168= variant is observed in 1 unaffected individual (Baylor Genetics internal database) (BS2_supporting). In summary, p.Val168= variant in TCF4 is classified as benign based on the ACMG/AMP criteria (BA1, BS2_supporting).
GeneDx	RCV000128380	SCV000171976	benign	not specified	2014-02-06	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago	RCV000128380	SCV000597416	likely benign	not specified	2015-11-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082033	SCV000646130	likely benign	Pitt-Hopkins syndrome	2024-01-29	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727317	SCV000707489	uncertain significance	not provided	2017-04-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316427	SCV000850628	likely benign	Inborn genetic diseases	2017-01-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003935209	SCV004748122	likely benign	TCF4-related disorder	2021-11-04	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).