Evidence Repository - Clinical Genome Resources

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

Variant: NM_001083962.1(TCF4):c.1826T>C (p.Leu609Pro)

CA16608769

393171 (ClinVar)

Gene: TCF4

Condition: Pitt-Hopkins syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 5d0fcac9-7b04-4d3f-92d8-91250132dcb7

HGVS expressions

NM_001083962.1:c.1826T>C

NM_001083962.1(TCF4):c.1826T>C (p.Leu609Pro)

ENST00000354452.8:c.1826T>C

ENST00000635822.2:c.1706T>C

ENST00000635990.2:n.1506T>C

ENST00000636400.2:c.1754T>C

ENST00000636751.2:c.*1534T>C

ENST00000636822.2:c.1436T>C

ENST00000637115.2:c.*1704T>C

ENST00000637169.2:c.1178T>C

ENST00000637239.2:n.1881T>C

ENST00000637250.2:n.1520T>C

ENST00000637923.2:n.1424T>C

ENST00000638154.3:c.1853T>C

ENST00000643689.1:c.1436T>C

ENST00000674764.1:c.*1437T>C

ENST00000675707.1:c.1436T>C

ENST00000354452.7:c.1826T>C

ENST00000356073.8:c.1814T>C

ENST00000398339.5:c.2132T>C

ENST00000457482.7:c.1346T>C

ENST00000537578.5:c.1754T>C

ENST00000537856.7:c.1424T>C

ENST00000540999.5:c.1742T>C

ENST00000543082.5:c.1688T>C

ENST00000544241.6:c.1613T>C

ENST00000561831.7:c.1334T>C

ENST00000561992.5:c.1424T>C

ENST00000562680.5:n.5349T>C

ENST00000564228.5:n.1601T>C

ENST00000564403.6:c.1844T>C

ENST00000564999.5:c.1814T>C

ENST00000565018.6:c.1562T>C

ENST00000566279.5:c.1646T>C

ENST00000566286.5:n.1805T>C

ENST00000567880.5:n.1634T>C

ENST00000568673.5:c.1754T>C

ENST00000568740.5:c.1739T>C

ENST00000570177.6:c.1424T>C

ENST00000570287.6:c.1334T>C

ENST00000616053.4:c.1562T>C

ENST00000626466.1:n.849T>C

ENST00000626584.2:c.1166T>C

ENST00000626631.1:n.56T>C

ENST00000629387.2:c.1826T>C

NM_001243226.2:c.2132T>C

NM_001243227.1:c.1754T>C

NM_001243228.1:c.1844T>C

NM_001243230.1:c.1805T>C

NM_001243231.1:c.1688T>C

NM_001243232.1:c.1613T>C

NM_001243233.1:c.1424T>C

NM_001243234.1:c.1346T>C

NM_001243235.1:c.1334T>C

NM_001243236.1:c.1334T>C

NM_001306207.1:c.1742T>C

NM_001306208.1:c.1601T>C

NM_003199.2:c.1814T>C

NM_001330604.2:c.1823T>C

NM_001330605.2:c.1436T>C

NM_001348211.1:c.1700T>C

NM_001348212.1:c.1424T>C

NM_001348213.1:c.1436T>C

NM_001348214.1:c.1331T>C

NM_001348215.1:c.1178T>C

NM_001348216.1:c.1346T>C

NM_001348217.1:c.1754T>C

NM_001348218.1:c.1754T>C

NM_001348219.1:c.1742T>C

NM_001348220.1:c.1739T>C

NM_001083962.2:c.1826T>C

NM_001243226.3:c.2132T>C

NM_001243227.2:c.1754T>C

NM_001243228.2:c.1844T>C

NM_001243231.2:c.1688T>C

NM_001243233.2:c.1424T>C

NM_001243234.2:c.1346T>C

NM_001243235.2:c.1334T>C

NM_001243236.2:c.1334T>C

NM_001330604.3:c.1823T>C

NM_001330605.3:c.1436T>C

NM_001348211.2:c.1700T>C

NM_001348212.2:c.1424T>C

NM_001348213.2:c.1436T>C

NM_001348214.2:c.1331T>C

NM_001348215.2:c.1178T>C

NM_001348216.2:c.1346T>C

NM_001348218.2:c.1754T>C

NM_001348219.2:c.1742T>C

NM_001369567.1:c.1826T>C

NM_001369568.1:c.1826T>C

NM_001369569.1:c.1823T>C

NM_001369570.1:c.1823T>C

NM_001369571.1:c.1814T>C

NM_001369572.1:c.1814T>C

NM_001369573.1:c.1811T>C

NM_001369574.1:c.1811T>C

NM_001369575.1:c.1754T>C

NM_001369576.1:c.1751T>C

NM_001369577.1:c.1751T>C

NM_001369578.1:c.1751T>C

NM_001369579.1:c.1751T>C

NM_001369580.1:c.1751T>C

NM_001369581.1:c.1751T>C

NM_001369582.1:c.1742T>C

NM_001369583.1:c.1742T>C

NM_001369584.1:c.1739T>C

NM_001369585.1:c.1739T>C

NM_001369586.1:c.1757T>C

NM_003199.3:c.1814T>C

NM_001243230.2:c.1805T>C

NC_000018.10:g.55228900A>G

CM000680.2:g.55228900A>G

NC_000018.9:g.52896131A>G

CM000680.1:g.52896131A>G

NC_000018.8:g.51047129A>G

NG_011716.1:g.364730T>C

NG_011716.2:g.412094T>C

Likely Pathogenic

PM2_Supporting PS2 PP3 PM1

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Leu609Pro variant in TCF4 occurs in the de novo state (biological parentage confirmed) in an affected individual (PS2). The p.Leu609Pro variant occurs in the well-characterized basic Helix-Loop-Helix domain (bHLH) functional domain of TCF4 (PM1). The p.Leu609Pro variant in TCF4 is absent from gnomAD (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.Leu609Pro variant in TCF4 is classified as likely pathogenic for Pitt-Hopkins syndrome based on the ACMG/AMP criteria (PS2, PM1, PM2_supporting, PP3).

PM2_Supporting

The p.Leu609Pro in TCF4 is absent from gnomAD.

PS2

The p.Leu609Pro variant in TCF4 occurs in the de novo state (biological parentage confirmed) in an affected individual

PP3

Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own

PM1

This variant is located in the basic Helix-Loop-Helix domain (bHLH)

Approved on: 2021-03-26

Published on: 2021-05-17

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