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.759C>G (p.Ser253Arg)

CA402701458

432062 (ClinVar)

Gene: TCF4

Condition: Pitt-Hopkins syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 1c53d5a5-faa3-4994-be9b-d5aef8d0405c

Approved on: 2021-03-26

Published on: 2021-05-17

HGVS expressions

NM_001083962.1:c.759C>G

NM_001083962.1(TCF4):c.759C>G (p.Ser253Arg)

ENST00000354452.8:c.759C>G

ENST00000630720.3:c.279C>G

ENST00000635822.2:c.759C>G

ENST00000635990.2:n.439C>G

ENST00000636400.2:c.687C>G

ENST00000636751.2:c.*467C>G

ENST00000636822.2:c.369C>G

ENST00000637115.2:c.*649C>G

ENST00000637169.2:c.111C>G

ENST00000637239.2:n.826C>G

ENST00000637250.2:n.453C>G

ENST00000637923.2:n.357C>G

ENST00000638154.3:c.789C>G

ENST00000643689.1:c.369C>G

ENST00000674764.1:c.*370C>G

ENST00000675707.1:c.369C>G

ENST00000354452.7:c.759C>G

ENST00000356073.8:c.759C>G

ENST00000398339.5:c.1065C>G

ENST00000457482.7:c.279C>G

ENST00000537578.5:c.687C>G

ENST00000537856.7:c.369C>G

ENST00000540999.5:c.687C>G

ENST00000543082.5:c.633C>G

ENST00000544241.6:c.546C>G

ENST00000561831.7:c.279C>G

ENST00000561992.5:c.369C>G

ENST00000562030.3:c.369C>G

ENST00000562607.5:c.369C>G

ENST00000562680.5:n.850C>G

ENST00000563686.5:n.614C>G

ENST00000563760.5:n.351C>G

ENST00000564228.5:n.546C>G

ENST00000564403.6:c.777C>G

ENST00000564999.5:c.759C>G

ENST00000565018.6:c.507C>G

ENST00000565580.3:n.508C>G

ENST00000566279.5:c.579C>G

ENST00000566286.5:n.753C>G

ENST00000566514.5:c.720C>G

ENST00000566777.5:c.369C>G

ENST00000567880.5:n.579C>G

ENST00000568169.5:c.771C>G

ENST00000568673.5:c.687C>G

ENST00000568740.5:c.684C>G

ENST00000569012.5:c.369C>G

ENST00000570146.3:n.23C>G

ENST00000570177.6:c.369C>G

ENST00000570287.6:c.279C>G

ENST00000616053.4:c.507C>G

ENST00000625849.2:n.619C>G

ENST00000625925.2:c.369C>G

ENST00000626584.2:c.111C>G

ENST00000627136.2:n.524-14116C>G

ENST00000628078.2:c.369C>G

ENST00000628636.2:c.369C>G

ENST00000628689.2:c.175+3902C>G

ENST00000629343.2:c.369C>G

ENST00000629387.2:c.759C>G

ENST00000630268.2:c.369C>G

ENST00000630319.2:c.528C>G

ENST00000630712.2:c.369C>G

ENST00000630720.2:c.279C>G

ENST00000630828.2:c.549C>G

NM_001243226.2:c.1065C>G

NM_001243227.1:c.687C>G

NM_001243228.1:c.777C>G

NM_001243230.1:c.753C>G

NM_001243231.1:c.633C>G

NM_001243232.1:c.546C>G

NM_001243233.1:c.369C>G

NM_001243234.1:c.279C>G

NM_001243235.1:c.279C>G

NM_001243236.1:c.279C>G

NM_001306207.1:c.687C>G

NM_001306208.1:c.546C>G

NM_003199.2:c.759C>G

NM_001330604.2:c.759C>G

NM_001330605.2:c.369C>G

NM_001348211.1:c.633C>G

NM_001348212.1:c.369C>G

NM_001348213.1:c.369C>G

NM_001348214.1:c.279C>G

NM_001348215.1:c.111C>G

NM_001348216.1:c.279C>G

NM_001348217.1:c.687C>G

NM_001348218.1:c.687C>G

NM_001348219.1:c.687C>G

NM_001348220.1:c.684C>G

NM_001083962.2:c.759C>G

NM_001243226.3:c.1065C>G

NM_001243227.2:c.687C>G

NM_001243228.2:c.777C>G

NM_001243231.2:c.633C>G

NM_001243233.2:c.369C>G

NM_001243234.2:c.279C>G

NM_001243235.2:c.279C>G

NM_001243236.2:c.279C>G

NM_001330604.3:c.759C>G

NM_001330605.3:c.369C>G

NM_001348211.2:c.633C>G

NM_001348212.2:c.369C>G

NM_001348213.2:c.369C>G

NM_001348214.2:c.279C>G

NM_001348215.2:c.111C>G

NM_001348216.2:c.279C>G

NM_001348218.2:c.687C>G

NM_001348219.2:c.687C>G

NM_001369567.1:c.759C>G

NM_001369568.1:c.759C>G

NM_001369569.1:c.756C>G

NM_001369570.1:c.756C>G

NM_001369571.1:c.759C>G

NM_001369572.1:c.759C>G

NM_001369573.1:c.756C>G

NM_001369574.1:c.759C>G

NM_001369575.1:c.687C>G

NM_001369576.1:c.684C>G

NM_001369577.1:c.687C>G

NM_001369578.1:c.684C>G

NM_001369579.1:c.687C>G

NM_001369580.1:c.687C>G

NM_001369581.1:c.684C>G

NM_001369582.1:c.687C>G

NM_001369583.1:c.687C>G

NM_001369584.1:c.684C>G

NM_001369585.1:c.684C>G

NM_001369586.1:c.687C>G

NM_003199.3:c.759C>G

NM_001243230.2:c.753C>G

NC_000018.10:g.55275649G>C

CM000680.2:g.55275649G>C

NC_000018.9:g.52942880G>C

CM000680.1:g.52942880G>C

NC_000018.8:g.51093878G>C

NG_011716.1:g.317981C>G

NG_011716.2:g.365345C>G

Likely Pathogenic

PM2_Supporting PM6_Strong PP4 PS4_Moderate

Evidence Links 2

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.Ser253Arg variant in TCF4 has been reported in at least 2 de novo occurrences (biological parentage unconfirmed) in individuals with Pitt–Hopkins syndrome (PMID 29322350; 26993267, described as p.Ser355Arg) (PM6_Strong). The p.Ser253Arg variant has been observed in 3 other individuals with Pitt-Hopkins syndrome (PMID 29322350; 26993267, described as p.Ser355Arg) (PS4_Moderate). The p.Ser253Arg variant in TCF4 is absent from gnomAD (PM2_Supporting). The p.Ser253Arg variant in TCF4 has been reported in an individual with a clinical phenotype suggestive of Pitt–Hopkins syndrome (PMID 26993267, described as p.Ser355Arg) (PP4). In summary, the p.Ser253Arg variant in TCF4 is classified as likely pathogenic for Pitt-Hopkins syndrome based on the ACMG/AMP criteria (PM6_strong, PS4_moderate, PM2_supporting, PP4).

PM2_Supporting

The p.Ser253Arg variant in TCF4 is absent from gnomAD.

PM6_Strong

The p.Ser253Arg variant in TCF4 has been reported in 1 unconfirmed de novo occurrence in an individual with a Rett syndrome-like presentation. PubMed:29322350

The p.Ser253Arg variant in TCF4 has been reported in 2 unconfirmed de novo occurrences in an individual with Pitt–Hopkins syndrome and in an individual with early infantile epileptic encephalopathy. PubMed:26993267

PP4

The p.Ser253Arg variant in TCF4 has been reported in an individual with a clinical phenotype suggestive of Pitt–Hopkins syndrome (PMID 26993267, described as p.Ser355Arg)

PS4_Moderate

The p.Ser253Arg variant has been observed in 3 other individuals with Pitt-Hopkins syndrome (PMID 29322350; 26993267, described as p.Ser355Arg)

Observed in 1 affected individual PubMed:29322350

Observed in 2 individuals with Pitt Hopkins syndrome PubMed:26993267

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