Variant: NM_001083962.2(TCF4):c.1283G>T (p.Gly428Val)

CA300814398

574403 (ClinVar)

Gene: TCF4

Condition: Pitt-Hopkins syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 10d8e8a7-ab23-4642-8e12-8f34edafb761

Approved on: 2025-06-25

Published on: 2025-06-30

HGVS expressions

NM_001083962.2:c.1283G>T
NM_001083962.2(TCF4):c.1283G>T (p.Gly428Val)
NC_000018.10:g.55254564C>A
CM000680.2:g.55254564C>A
NC_000018.9:g.52921795C>A
CM000680.1:g.52921795C>A
NC_000018.8:g.51072793C>A
NG_011716.1:g.339066G>T
NG_011716.2:g.386430G>T
ENST00000354452.8:c.1283G>T
ENST00000630720.3:c.800G>T
ENST00000635822.2:c.1283G>T
ENST00000635990.2:n.963G>T
ENST00000636400.2:c.1211G>T
ENST00000636751.2:c.*991G>T
ENST00000636822.2:c.893G>T
ENST00000637115.2:c.*1173G>T
ENST00000637169.2:c.635G>T
ENST00000637239.2:n.1350G>T
ENST00000637250.2:n.977G>T
ENST00000637923.2:c.881G>T
ENST00000638154.3:c.1310G>T
ENST00000643689.1:c.893G>T
ENST00000674764.1:c.*894G>T
ENST00000675707.1:c.893G>T
ENST00000354452.7:c.1283G>T
ENST00000356073.8:c.1283G>T
ENST00000398339.5:c.1589G>T
ENST00000457482.7:c.803G>T
ENST00000537578.5:c.1211G>T
ENST00000537856.7:c.893G>T
ENST00000540999.5:c.1211G>T
ENST00000543082.5:c.1157G>T
ENST00000544241.6:c.1070G>T
ENST00000561831.7:c.803G>T
ENST00000561992.5:c.893G>T
ENST00000562680.5:n.1374G>T
ENST00000563760.5:n.796G>T
ENST00000564228.5:c.1070G>T
ENST00000564403.6:c.1301G>T
ENST00000564999.5:c.1283G>T
ENST00000565018.6:c.1031G>T
ENST00000566279.5:c.1103G>T
ENST00000566286.5:c.1274G>T
ENST00000567880.5:c.1103G>T
ENST00000568673.5:c.1211G>T
ENST00000568740.5:c.1208G>T
ENST00000570177.6:c.893G>T
ENST00000570287.6:c.803G>T
ENST00000616053.4:c.1031G>T
ENST00000626466.1:n.318G>T
ENST00000626584.2:c.635G>T
ENST00000629387.2:c.1283G>T
ENST00000630720.2:c.800G>T
NM_001083962.1:c.1283G>T
NM_001243226.2:c.1589G>T
NM_001243227.1:c.1211G>T
NM_001243228.1:c.1301G>T
NM_001243230.1:c.1274G>T
NM_001243231.1:c.1157G>T
NM_001243232.1:c.1070G>T
NM_001243233.1:c.893G>T
NM_001243234.1:c.803G>T
NM_001243235.1:c.803G>T
NM_001243236.1:c.803G>T
NM_001306207.1:c.1211G>T
NM_001306208.1:c.1070G>T
NM_003199.2:c.1283G>T
NM_001330604.2:c.1280G>T
NM_001330605.2:c.893G>T
NM_001348211.1:c.1157G>T
NM_001348212.1:c.893G>T
NM_001348213.1:c.893G>T
NM_001348214.1:c.800G>T
NM_001348215.1:c.635G>T
NM_001348216.1:c.803G>T
NM_001348217.1:c.1211G>T
NM_001348218.1:c.1211G>T
NM_001348219.1:c.1211G>T
NM_001348220.1:c.1208G>T
NM_001243226.3:c.1589G>T
NM_001243227.2:c.1211G>T
NM_001243228.2:c.1301G>T
NM_001243231.2:c.1157G>T
NM_001243233.2:c.893G>T
NM_001243234.2:c.803G>T
NM_001243235.2:c.803G>T
NM_001243236.2:c.803G>T
NM_001330604.3:c.1280G>T
NM_001330605.3:c.893G>T
NM_001348211.2:c.1157G>T
NM_001348212.2:c.893G>T
NM_001348213.2:c.893G>T
NM_001348214.2:c.800G>T
NM_001348215.2:c.635G>T
NM_001348216.2:c.803G>T
NM_001348218.2:c.1211G>T
NM_001348219.2:c.1211G>T
NM_001369567.1:c.1283G>T
NM_001369568.1:c.1283G>T
NM_001369569.1:c.1280G>T
NM_001369570.1:c.1280G>T
NM_001369571.1:c.1283G>T
NM_001369572.1:c.1283G>T
NM_001369573.1:c.1280G>T
NM_001369574.1:c.1280G>T
NM_001369575.1:c.1211G>T
NM_001369576.1:c.1208G>T
NM_001369577.1:c.1208G>T
NM_001369578.1:c.1208G>T
NM_001369579.1:c.1208G>T
NM_001369580.1:c.1208G>T
NM_001369581.1:c.1208G>T
NM_001369582.1:c.1211G>T
NM_001369583.1:c.1211G>T
NM_001369584.1:c.1208G>T
NM_001369585.1:c.1208G>T
NM_001369586.1:c.1214G>T
NM_003199.3:c.1283G>T
NM_001243230.2:c.1274G>T

Benign

• Met criteria codes: BS2 BS1

• Not Met criteria codes: BP4 PP3 PS4 PM2

Expert Panel

Rett and Angelman-like Disorders VCEP

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

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The highest population minor allele frequency of the p.Gly428Val variant in TCF4 in gnomAD v4.1 is 0.0001001 in the Admixed American population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.00008) for BS1, and therefore meets this criterion (BS1). The p.Gly428Val variant is observed in at least 2 unaffected individuals (internal database - Ambry Genetics) (BS2). In summary, the p.Gly428Val variant in TCF4 is classified as benign based on the ACMG/AMP criteria (BS1, BS2). (TCF4 Specifications v.4.0; curation approved on [06/25/2025])

Met criteria codes

• BS2: The p.Gly428Val variant is observed in at least 2 unaffected individuals (internal database - Ambry Genetics) (BS2).
• BS1: The highest population minor allele frequency of the p.Gly428Val variant in TCF4 in gnomAD v4.1 is 0.0001001 in the Admixed American population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.00008) for BS1, and therefore meets this criterion (BS1).

Not Met criteria codes

• BP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: The p.Gly428Val variant in TCF4 has not been reported in individuals with Pitt-Hopkins syndrome.
• PM2: The p.Gly428Val variant in TCF4 is present in gnomAD (3 alleles).