Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001083962.2(TCF4):c.1086G>A (p.Trp362Ter)

CA266818

93540 (ClinVar)

Gene: TCF4 (HGNC:6925)
Condition: Pitt-Hopkins syndrome (MONDO:0012589)
Inheritance Mode: Autosomal dominant inheritance
UUID: 0318c444-bec7-4c3c-b7be-61b4e0c8ba2a
Approved on: 2026-04-23
Published on: 2026-06-19

HGVS expressions

NM_001083962.2:c.1086G>A
NM_001083962.2(TCF4):c.1086G>A (p.Trp362Ter)
NC_000018.10:g.55257375C>T
CM000680.2:g.55257375C>T
NC_000018.9:g.52924606C>T
CM000680.1:g.52924606C>T
NC_000018.8:g.51075604C>T
NG_011716.1:g.336255G>A
NG_011716.2:g.383619G>A
ENST00000354452.8:c.1086G>A
ENST00000630720.3:c.603G>A
ENST00000635822.2:c.1086G>A
ENST00000635990.2:n.766G>A
ENST00000636400.2:c.1014G>A
ENST00000636751.2:c.*794G>A
ENST00000636822.2:c.696G>A
ENST00000637115.2:c.*976G>A
ENST00000637169.2:c.438G>A
ENST00000637239.2:n.1153G>A
ENST00000637250.2:n.780G>A
ENST00000637923.2:c.684G>A
ENST00000638154.3:c.1113G>A
ENST00000643689.1:c.696G>A
ENST00000674764.1:c.*697G>A
ENST00000675707.1:c.696G>A
ENST00000354452.7:c.1086G>A
ENST00000356073.8:c.1086G>A
ENST00000398339.5:c.1392G>A
ENST00000457482.7:c.606G>A
ENST00000537578.5:c.1014G>A
ENST00000537856.7:c.696G>A
ENST00000540999.5:c.1014G>A
ENST00000543082.5:c.960G>A
ENST00000544241.6:c.873G>A
ENST00000561831.7:c.606G>A
ENST00000561992.5:c.696G>A
ENST00000562680.5:n.1177G>A
ENST00000563760.5:n.599G>A
ENST00000564228.5:c.873G>A
ENST00000564403.6:c.1104G>A
ENST00000564999.5:c.1086G>A
ENST00000565018.6:c.834G>A
ENST00000566279.5:c.906G>A
ENST00000566286.5:c.1077G>A
ENST00000567880.5:c.906G>A
ENST00000568673.5:c.1014G>A
ENST00000568740.5:c.1011G>A
ENST00000570177.6:c.696G>A
ENST00000570287.6:c.606G>A
ENST00000616053.4:c.834G>A
ENST00000626466.1:n.121G>A
ENST00000626584.2:c.438G>A
ENST00000628689.2:c.*229G>A
ENST00000629343.2:c.696G>A
ENST00000629387.2:c.1086G>A
ENST00000630720.2:c.603G>A
NM_001083962.1:c.1086G>A
NM_001243226.2:c.1392G>A
NM_001243227.1:c.1014G>A
NM_001243228.1:c.1104G>A
NM_001243230.1:c.1077G>A
NM_001243231.1:c.960G>A
NM_001243232.1:c.873G>A
NM_001243233.1:c.696G>A
NM_001243234.1:c.606G>A
NM_001243235.1:c.606G>A
NM_001243236.1:c.606G>A
NM_001306207.1:c.1014G>A
NM_001306208.1:c.873G>A
NM_003199.2:c.1086G>A
NM_001330604.2:c.1083G>A
NM_001330605.2:c.696G>A
NM_001348211.1:c.960G>A
NM_001348212.1:c.696G>A
NM_001348213.1:c.696G>A
NM_001348214.1:c.603G>A
NM_001348215.1:c.438G>A
NM_001348216.1:c.606G>A
NM_001348217.1:c.1014G>A
NM_001348218.1:c.1014G>A
NM_001348219.1:c.1014G>A
NM_001348220.1:c.1011G>A
NM_001243226.3:c.1392G>A
NM_001243227.2:c.1014G>A
NM_001243228.2:c.1104G>A
NM_001243231.2:c.960G>A
NM_001243233.2:c.696G>A
NM_001243234.2:c.606G>A
NM_001243235.2:c.606G>A
NM_001243236.2:c.606G>A
NM_001330604.3:c.1083G>A
NM_001330605.3:c.696G>A
NM_001348211.2:c.960G>A
NM_001348212.2:c.696G>A
NM_001348213.2:c.696G>A
NM_001348214.2:c.603G>A
NM_001348215.2:c.438G>A
NM_001348216.2:c.606G>A
NM_001348218.2:c.1014G>A
NM_001348219.2:c.1014G>A
NM_001369567.1:c.1086G>A
NM_001369568.1:c.1086G>A
NM_001369569.1:c.1083G>A
NM_001369570.1:c.1083G>A
NM_001369571.1:c.1086G>A
NM_001369572.1:c.1086G>A
NM_001369573.1:c.1083G>A
NM_001369574.1:c.1083G>A
NM_001369575.1:c.1014G>A
NM_001369576.1:c.1011G>A
NM_001369577.1:c.1011G>A
NM_001369578.1:c.1011G>A
NM_001369579.1:c.1011G>A
NM_001369580.1:c.1011G>A
NM_001369581.1:c.1011G>A
NM_001369582.1:c.1014G>A
NM_001369583.1:c.1014G>A
NM_001369584.1:c.1011G>A
NM_001369585.1:c.1011G>A
NM_001369586.1:c.1017G>A
NM_003199.3:c.1086G>A
NM_001243230.2:c.1077G>A
More

Likely Pathogenic

Met criteria codes 2
PVS1 PM2_Supporting
Not Met criteria codes 1
PP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TCF4 Version 5.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The p.Trp362Ter variant in TCF4 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a TCF4 where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the TCF4 is pathogenic (PVS1). The p.Trp362Ter variant in TCF4 is absent from gnomAD (PM2_Supporting). In summary, the p.Trp362Ter variant in TCF4 is classified as likely pathogenic for Pitt-Hopkins syndrome based on the ACMG/AMP criteria (PVS1, PM2_supporting). (TCF4 Specifications v5.0.0; curation approved on 4/23/2026).
Met criteria codes
PVS1
The p.Trp362Ter variant in TCF4 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a TCF4 where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the TCF4 is pathogenic.
PM2_Supporting
The p.Trp362Ter variant in TCF4 is absent from gnomAD.
Not Met criteria codes
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
ClinGen Terms of Use.
¤ Powered by BCM's Genboree.