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.1774G>A (p.Gly592Ser)

CA8970151

598113 (ClinVar)

Gene: TCF4 (HGNC:6925)
Condition: Pitt-Hopkins syndrome (MONDO:0012589)
Inheritance Mode: Autosomal dominant inheritance
UUID: f61eb051-8b88-40ab-83be-8229d724edd6
Approved on: 2024-08-30
Published on: 2024-12-13

HGVS expressions

NM_001083962.2:c.1774G>A
NM_001083962.2(TCF4):c.1774G>A (p.Gly592Ser)
NC_000018.10:g.55228952C>T
CM000680.2:g.55228952C>T
NC_000018.9:g.52896183C>T
CM000680.1:g.52896183C>T
NC_000018.8:g.51047181C>T
NG_011716.1:g.364678G>A
NG_011716.2:g.412042G>A
ENST00000354452.8:c.1774G>A
ENST00000635822.2:c.1654G>A
ENST00000635990.2:n.1454G>A
ENST00000636400.2:c.1702G>A
ENST00000636751.2:c.*1482G>A
ENST00000636822.2:c.1384G>A
ENST00000637115.2:c.*1652G>A
ENST00000637169.2:c.1126G>A
ENST00000637239.2:n.1829G>A
ENST00000637250.2:n.1468G>A
ENST00000637923.2:c.1372G>A
ENST00000638154.3:c.1801G>A
ENST00000643689.1:c.1384G>A
ENST00000674764.1:c.*1385G>A
ENST00000675707.1:c.1384G>A
ENST00000354452.7:c.1774G>A
ENST00000356073.8:c.1762G>A
ENST00000398339.5:c.2080G>A
ENST00000457482.7:c.1294G>A
ENST00000537578.5:c.1702G>A
ENST00000537856.7:c.1372G>A
ENST00000540999.5:c.1690G>A
ENST00000543082.5:c.1636G>A
ENST00000544241.6:c.1561G>A
ENST00000561831.7:c.1282G>A
ENST00000561992.5:c.1372G>A
ENST00000562680.5:n.5297G>A
ENST00000564228.5:c.1549G>A
ENST00000564403.6:c.1792G>A
ENST00000564999.5:c.1762G>A
ENST00000565018.6:c.1510G>A
ENST00000566279.5:c.1594G>A
ENST00000566286.5:c.1753G>A
ENST00000567880.5:c.1582G>A
ENST00000568673.5:c.1702G>A
ENST00000568740.5:c.1687G>A
ENST00000570177.6:c.1372G>A
ENST00000570287.6:c.1282G>A
ENST00000616053.4:c.1510G>A
ENST00000626466.1:n.797G>A
ENST00000626584.2:c.1114G>A
ENST00000626631.1:c.4G>A
ENST00000629387.2:c.1774G>A
NM_001083962.1:c.1774G>A
NM_001243226.2:c.2080G>A
NM_001243227.1:c.1702G>A
NM_001243228.1:c.1792G>A
NM_001243230.1:c.1753G>A
NM_001243231.1:c.1636G>A
NM_001243232.1:c.1561G>A
NM_001243233.1:c.1372G>A
NM_001243234.1:c.1294G>A
NM_001243235.1:c.1282G>A
NM_001243236.1:c.1282G>A
NM_001306207.1:c.1690G>A
NM_001306208.1:c.1549G>A
NM_003199.2:c.1762G>A
NM_001330604.2:c.1771G>A
NM_001330605.2:c.1384G>A
NM_001348211.1:c.1648G>A
NM_001348212.1:c.1372G>A
NM_001348213.1:c.1384G>A
NM_001348214.1:c.1279G>A
NM_001348215.1:c.1126G>A
NM_001348216.1:c.1294G>A
NM_001348217.1:c.1702G>A
NM_001348218.1:c.1702G>A
NM_001348219.1:c.1690G>A
NM_001348220.1:c.1687G>A
NM_001243226.3:c.2080G>A
NM_001243227.2:c.1702G>A
NM_001243228.2:c.1792G>A
NM_001243231.2:c.1636G>A
NM_001243233.2:c.1372G>A
NM_001243234.2:c.1294G>A
NM_001243235.2:c.1282G>A
NM_001243236.2:c.1282G>A
NM_001330604.3:c.1771G>A
NM_001330605.3:c.1384G>A
NM_001348211.2:c.1648G>A
NM_001348212.2:c.1372G>A
NM_001348213.2:c.1384G>A
NM_001348214.2:c.1279G>A
NM_001348215.2:c.1126G>A
NM_001348216.2:c.1294G>A
NM_001348218.2:c.1702G>A
NM_001348219.2:c.1690G>A
NM_001369567.1:c.1774G>A
NM_001369568.1:c.1774G>A
NM_001369569.1:c.1771G>A
NM_001369570.1:c.1771G>A
NM_001369571.1:c.1762G>A
NM_001369572.1:c.1762G>A
NM_001369573.1:c.1759G>A
NM_001369574.1:c.1759G>A
NM_001369575.1:c.1702G>A
NM_001369576.1:c.1699G>A
NM_001369577.1:c.1699G>A
NM_001369578.1:c.1699G>A
NM_001369579.1:c.1699G>A
NM_001369580.1:c.1699G>A
NM_001369581.1:c.1699G>A
NM_001369582.1:c.1690G>A
NM_001369583.1:c.1690G>A
NM_001369584.1:c.1687G>A
NM_001369585.1:c.1687G>A
NM_001369586.1:c.1705G>A
NM_003199.3:c.1762G>A
NM_001243230.2:c.1753G>A
More

Likely Pathogenic

Met criteria codes 3
PP1 PM1 PS2
Not Met criteria codes 3
BA1 PM2 BS1

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 3.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The p.Gly592Ser variant in TCF4 has been reported as a de novo occurrence (biological parentage confirmed) in an individual with a neurodevelopmental disorder (internal database - GeneDx) (PS2). The p.Gly592Ser variant occurs in the well-characterized Basic Helix-Loop-Helix domain (bHLH) (aa 564-617) functional domain of the TCF4 (PM1). The variant has been reported to segregate in three informative meioses (internal database - GeneDx) with limited clinical information provided (PP1). The highest population minor allele frequency of the p.Gly592Ser variant in TCF4 in gnomAD v4.1 is 8.474e-7 (1/1180018 alleles) in European (non-Finnish) population (not sufficient to meet BS1 criteria). Of note, this variant was observed once in gnomAD v4.1. In summary, the p.Gly592Ser variant in TCF4 is classified as likely pathogenic for Pitt-Hopkins syndrome based on the ACMG/AMP criteria (PS2, PM1, PP1). (TCF4 specification v.3; approved on 8/30/2024)
Met criteria codes
PP1
The variant has been reported to segregate in three informative meioses (internal database - GeneDx) with limited clinical information provided (PP1).
PM1
The p.Gly592Ser variant occurs in the well-characterized Basic Helix-Loop-Helix domain (bHLH) (aa 564-617) functional domain of TCF4 (PM1).
PS2
The p.Gly592Ser variant in TCF4 has been reported as a de novo occurrence (biological parentage confirmed) in an individual with a neurodevelopmental disorder (internal database - GeneDx).
Not Met criteria codes
BA1
The highest population minor allele frequency of the p.Gly592Ser variant in TCF4 in gnomAD v4.1 is 8.474e-7 (1/1180018 alleles) in European (non-Finnish) population (not sufficient to meet BA1 criteria).
PM2
The highest population minor allele frequency of the p.Gly592Ser variant in TCF4 in gnomAD v4.1 is 8.474e-7 (1/1180018 alleles) in European (non-Finnish) population (not sufficient to meet PM2 criteria).
BS1
The highest population minor allele frequency of the p.Gly592Ser variant in TCF4 in gnomAD v4.1 is 8.474e-7 (1/1180018 alleles) in European (non-Finnish) population (not sufficient to meet BS1 criteria).
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.