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.1817C>T (p.Thr606Ile)

CA402528512

1164050 (ClinVar)

Gene: TCF4 (HGNC:6925)
Condition: Pitt-Hopkins syndrome (MONDO:0012589)
Inheritance Mode: Autosomal dominant inheritance
UUID: f6d6c268-b8c3-422c-bafc-9dde1cd92932
Approved on: 2025-05-07
Published on: 2025-06-30

HGVS expressions

NM_001083962.2:c.1817C>T
NM_001083962.2(TCF4):c.1817C>T (p.Thr606Ile)
NC_000018.10:g.55228909G>A
CM000680.2:g.55228909G>A
NC_000018.9:g.52896140G>A
CM000680.1:g.52896140G>A
NC_000018.8:g.51047138G>A
NG_011716.1:g.364721C>T
NG_011716.2:g.412085C>T
ENST00000354452.8:c.1817C>T
ENST00000635822.2:c.1697C>T
ENST00000635990.2:n.1497C>T
ENST00000636400.2:c.1745C>T
ENST00000636751.2:c.*1525C>T
ENST00000636822.2:c.1427C>T
ENST00000637115.2:c.*1695C>T
ENST00000637169.2:c.1169C>T
ENST00000637239.2:n.1872C>T
ENST00000637250.2:n.1511C>T
ENST00000637923.2:c.1415C>T
ENST00000638154.3:c.1844C>T
ENST00000643689.1:c.1427C>T
ENST00000674764.1:c.*1428C>T
ENST00000675707.1:c.1427C>T
ENST00000354452.7:c.1817C>T
ENST00000356073.8:c.1805C>T
ENST00000398339.5:c.2123C>T
ENST00000457482.7:c.1337C>T
ENST00000537578.5:c.1745C>T
ENST00000537856.7:c.1415C>T
ENST00000540999.5:c.1733C>T
ENST00000543082.5:c.1679C>T
ENST00000544241.6:c.1604C>T
ENST00000561831.7:c.1325C>T
ENST00000561992.5:c.1415C>T
ENST00000562680.5:n.5340C>T
ENST00000564228.5:c.1592C>T
ENST00000564403.6:c.1835C>T
ENST00000564999.5:c.1805C>T
ENST00000565018.6:c.1553C>T
ENST00000566279.5:c.1637C>T
ENST00000566286.5:c.1796C>T
ENST00000567880.5:c.1625C>T
ENST00000568673.5:c.1745C>T
ENST00000568740.5:c.1730C>T
ENST00000570177.6:c.1415C>T
ENST00000570287.6:c.1325C>T
ENST00000616053.4:c.1553C>T
ENST00000626466.1:n.840C>T
ENST00000626584.2:c.1157C>T
ENST00000626631.1:c.47C>T
ENST00000629387.2:c.1817C>T
NM_001083962.1:c.1817C>T
NM_001243226.2:c.2123C>T
NM_001243227.1:c.1745C>T
NM_001243228.1:c.1835C>T
NM_001243230.1:c.1796C>T
NM_001243231.1:c.1679C>T
NM_001243232.1:c.1604C>T
NM_001243233.1:c.1415C>T
NM_001243234.1:c.1337C>T
NM_001243235.1:c.1325C>T
NM_001243236.1:c.1325C>T
NM_001306207.1:c.1733C>T
NM_001306208.1:c.1592C>T
NM_003199.2:c.1805C>T
NM_001330604.2:c.1814C>T
NM_001330605.2:c.1427C>T
NM_001348211.1:c.1691C>T
NM_001348212.1:c.1415C>T
NM_001348213.1:c.1427C>T
NM_001348214.1:c.1322C>T
NM_001348215.1:c.1169C>T
NM_001348216.1:c.1337C>T
NM_001348217.1:c.1745C>T
NM_001348218.1:c.1745C>T
NM_001348219.1:c.1733C>T
NM_001348220.1:c.1730C>T
NM_001243226.3:c.2123C>T
NM_001243227.2:c.1745C>T
NM_001243228.2:c.1835C>T
NM_001243231.2:c.1679C>T
NM_001243233.2:c.1415C>T
NM_001243234.2:c.1337C>T
NM_001243235.2:c.1325C>T
NM_001243236.2:c.1325C>T
NM_001330604.3:c.1814C>T
NM_001330605.3:c.1427C>T
NM_001348211.2:c.1691C>T
NM_001348212.2:c.1415C>T
NM_001348213.2:c.1427C>T
NM_001348214.2:c.1322C>T
NM_001348215.2:c.1169C>T
NM_001348216.2:c.1337C>T
NM_001348218.2:c.1745C>T
NM_001348219.2:c.1733C>T
NM_001369567.1:c.1817C>T
NM_001369568.1:c.1817C>T
NM_001369569.1:c.1814C>T
NM_001369570.1:c.1814C>T
NM_001369571.1:c.1805C>T
NM_001369572.1:c.1805C>T
NM_001369573.1:c.1802C>T
NM_001369574.1:c.1802C>T
NM_001369575.1:c.1745C>T
NM_001369576.1:c.1742C>T
NM_001369577.1:c.1742C>T
NM_001369578.1:c.1742C>T
NM_001369579.1:c.1742C>T
NM_001369580.1:c.1742C>T
NM_001369581.1:c.1742C>T
NM_001369582.1:c.1733C>T
NM_001369583.1:c.1733C>T
NM_001369584.1:c.1730C>T
NM_001369585.1:c.1730C>T
NM_001369586.1:c.1748C>T
NM_003199.3:c.1805C>T
NM_001243230.2:c.1796C>T
More

Likely Pathogenic

Met criteria codes 4
PM1 PS2 PM2_Supporting PP3

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 4.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The p.Thr606Ile variant in TCF4 has been reported as a de novo occurrence (biological parentage confirmed) in an individual with global developmental delay, epilepsy, ventriculomegaly, and dysmorphic facial features (PMID 34580403) (PS2). The p.Thr606Ile variant occurs in the well-characterized Basic Helix-Loop-Helix functional domain of the TCF4 gene (PM1). The p.Thr606Ile variant in TCF4 is absent from gnomAD v4.1 (PM2_Supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, the p.Thr606Ile variant in TCF4 is classified as likely pathogenic for Pitt-Hopkins syndrome based on the ACMG/AMP criteria (PS2, PM1, PM2_supporting, PP3). (TCF4 Specifications v4.0; curation approved on [5/7/2025])
Met criteria codes
PM1
The p.Thr606Ile variant occurs in the well-characterized Basic Helix-Loop-Helix functional domain of the TCF4 gene (PM1).
PS2
The p.Thr606Ile variant in TCF4 has been reported as a de novo occurrence (biological parentage confirmed) in an individual with global developmental delay, epilepsy, ventriculomegaly, and dysmorphic facial features (PMID 34580403).
PM2_Supporting
The p.Thr606Ile variant in TCF4 is absent from gnomAD v4.1 (PM2_Supporting).
PP3
Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3).
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.