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]
Link to SEPIO compliant JSON-LD document
  • See Evidence submitted by expert panel for details.

Variant: NM_001083962.1(TCF4):c.1086G>A (p.Trp362Ter)

CA266818

93540 (ClinVar)

Gene: TCF4
Condition: Pitt-Hopkins syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 0318c444-bec7-4c3c-b7be-61b4e0c8ba2a

HGVS expressions

NM_001083962.1:c.1086G>A
NM_001083962.1(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
ENST00000354452.7: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
ENST00000564228.5:n.873G>A
ENST00000564403.6:c.1104G>A
ENST00000564999.5:c.1086G>A
ENST00000565018.6:c.834G>A
ENST00000566279.5:c.906G>A
ENST00000566286.5:n.1077G>A
ENST00000567880.5:n.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
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_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_001083962.2:c.1086G>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

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"
Met criteria codes 2
PM2_Supporting PVS1
Not Met criteria codes 1
PP4

Evidence Links 0

Expert Panel

Criteria Specification Information

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 based on the ACMG/AMP criteria (PVS1, PM2_supporting).
Met criteria codes
PM2_Supporting
The p.Trp362Ter variant in TCF4 is absent from gnomAD
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
Not Met criteria codes
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2021-04-02
Published on: 2021-04-19
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