Submissions for variant NM_001083962.2(TCF4):c.944C>T (p.Ala315Val)

gnomAD frequency: 0.00066  dbSNP: rs147445499

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV001084639	SCV001711969	benign	Pitt-Hopkins syndrome	2021-03-26	reviewed by expert panel	curation	The allele frequency of the p.Ala315Val variant in TCF4 is 0.1% 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.Ala315Val variant is observed in at least 2 unaffected individuals (internal database) (BS2). The p.Ala315Val variant is found in a patient with an alternate molecular basis of disease (internal database) (BP5). In summary, the p.Ala315Val variant in TCF4 is classified as benign based on the ACMG/AMP criteria (BA1, BS2, BP5).
Genetic Services Laboratory, University of Chicago	RCV000147729	SCV000195194	benign	not specified	2013-02-08	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000147729	SCV000225558	benign	not specified	2016-04-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000147729	SCV000243360	benign	not specified	2016-06-24	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.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000147729	SCV000257775	benign	not specified	2015-02-16	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000422948	SCV000511437	likely benign	not provided	2017-01-05	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084639	SCV000646139	likely benign	Pitt-Hopkins syndrome	2025-01-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316955	SCV000850850	likely benign	Inborn genetic diseases	2024-11-12	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.
Illumina Laboratory Services, Illumina	RCV001084639	SCV001284502	benign	Pitt-Hopkins syndrome	2017-08-14	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000422948	SCV004143136	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	TCF4: PP2, BS1
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000422948	SCV005875385	likely benign	not provided	2024-05-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003965112	SCV004784342	likely benign	TCF4-related disorder	2021-04-06	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).