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]

Variant: NM_001083962.2(TCF4):c.706C>G (p.Pro236Ala)

CA16043067

373746 (ClinVar)

Gene: TCF4 (HGNC:6925)

Condition: Pitt-Hopkins syndrome (MONDO:0012589)

Inheritance Mode: Autosomal dominant inheritance

UUID: a94a40b0-3f10-4035-8a9f-54bedbf96d01

Approved on: 2024-06-25

Published on: 2024-08-23

HGVS expressions

NM_001083962.2(TCF4):c.706C>G (p.Pro236Ala)

NM_001083962.2:c.706C>G

NC_000018.10:g.55275702G>C

CM000680.2:g.55275702G>C

NC_000018.9:g.52942933G>C

CM000680.1:g.52942933G>C

NC_000018.8:g.51093931G>C

NG_011716.1:g.317928C>G

NG_011716.2:g.365292C>G

ENST00000354452.8:c.706C>G

ENST00000630720.3:c.226C>G

ENST00000635822.2:c.706C>G

ENST00000635990.2:n.386C>G

ENST00000636400.2:c.634C>G

ENST00000636751.2:c.*414C>G

ENST00000636822.2:c.316C>G

ENST00000637115.2:c.*596C>G

ENST00000637169.2:c.58C>G

ENST00000637239.2:n.773C>G

ENST00000637250.2:n.400C>G

ENST00000637923.2:c.304C>G

ENST00000638154.3:c.736C>G

ENST00000643689.1:c.316C>G

ENST00000674764.1:c.*317C>G

ENST00000675707.1:c.316C>G

ENST00000354452.7:c.706C>G

ENST00000356073.8:c.706C>G

ENST00000398339.5:c.1012C>G

ENST00000457482.7:c.226C>G

ENST00000537578.5:c.634C>G

ENST00000537856.7:c.316C>G

ENST00000540999.5:c.634C>G

ENST00000543082.5:c.580C>G

ENST00000544241.6:c.493C>G

ENST00000561831.7:c.226C>G

ENST00000561992.5:c.316C>G

ENST00000562030.3:c.316C>G

ENST00000562607.5:c.316C>G

ENST00000562638.5:c.316C>G

ENST00000562680.5:n.797C>G

ENST00000563686.5:n.561C>G

ENST00000563760.5:n.298C>G

ENST00000564228.5:c.493C>G

ENST00000564403.6:c.724C>G

ENST00000564999.5:c.706C>G

ENST00000565018.6:c.454C>G

ENST00000565580.3:n.455C>G

ENST00000566279.5:c.526C>G

ENST00000566286.5:c.700C>G

ENST00000566514.5:c.667C>G

ENST00000566777.5:c.316C>G

ENST00000567880.5:c.526C>G

ENST00000568169.5:c.718C>G

ENST00000568186.5:c.316C>G

ENST00000568673.5:c.634C>G

ENST00000568740.5:c.631C>G

ENST00000569012.5:c.316C>G

ENST00000570177.6:c.316C>G

ENST00000570287.6:c.226C>G

ENST00000616053.4:c.454C>G

ENST00000625849.2:n.566C>G

ENST00000625925.2:c.316C>G

ENST00000626584.2:c.58C>G

ENST00000627136.2:n.524-14169C>G

ENST00000628078.2:c.316C>G

ENST00000628636.2:c.316C>G

ENST00000628689.2:c.175+3849C>G

ENST00000629343.2:c.316C>G

ENST00000629387.2:c.706C>G

ENST00000630268.2:c.316C>G

ENST00000630319.2:c.475C>G

ENST00000630712.2:c.316C>G

ENST00000630720.2:c.226C>G

ENST00000630828.2:c.496C>G

ENST00000631043.2:n.505C>G

NM_001083962.1:c.706C>G

NM_001243226.2:c.1012C>G

NM_001243227.1:c.634C>G

NM_001243228.1:c.724C>G

NM_001243230.1:c.700C>G

NM_001243231.1:c.580C>G

NM_001243232.1:c.493C>G

NM_001243233.1:c.316C>G

NM_001243234.1:c.226C>G

NM_001243235.1:c.226C>G

NM_001243236.1:c.226C>G

NM_001306207.1:c.634C>G

NM_001306208.1:c.493C>G

NM_003199.2:c.706C>G

NM_001330604.2:c.706C>G

NM_001330605.2:c.316C>G

NM_001348211.1:c.580C>G

NM_001348212.1:c.316C>G

NM_001348213.1:c.316C>G

NM_001348214.1:c.226C>G

NM_001348215.1:c.58C>G

NM_001348216.1:c.226C>G

NM_001348217.1:c.634C>G

NM_001348218.1:c.634C>G

NM_001348219.1:c.634C>G

NM_001348220.1:c.631C>G

NM_001243226.3:c.1012C>G

NM_001243227.2:c.634C>G

NM_001243228.2:c.724C>G

NM_001243231.2:c.580C>G

NM_001243233.2:c.316C>G

NM_001243234.2:c.226C>G

NM_001243235.2:c.226C>G

NM_001243236.2:c.226C>G

NM_001330604.3:c.706C>G

NM_001330605.3:c.316C>G

NM_001348211.2:c.580C>G

NM_001348212.2:c.316C>G

NM_001348213.2:c.316C>G

NM_001348214.2:c.226C>G

NM_001348215.2:c.58C>G

NM_001348216.2:c.226C>G

NM_001348218.2:c.634C>G

NM_001348219.2:c.634C>G

NM_001369567.1:c.706C>G

NM_001369568.1:c.706C>G

NM_001369569.1:c.703C>G

NM_001369570.1:c.703C>G

NM_001369571.1:c.706C>G

NM_001369572.1:c.706C>G

NM_001369573.1:c.703C>G

NM_001369574.1:c.706C>G

NM_001369575.1:c.634C>G

NM_001369576.1:c.631C>G

NM_001369577.1:c.634C>G

NM_001369578.1:c.631C>G

NM_001369579.1:c.634C>G

NM_001369580.1:c.634C>G

NM_001369581.1:c.631C>G

NM_001369582.1:c.634C>G

NM_001369583.1:c.634C>G

NM_001369584.1:c.631C>G

NM_001369585.1:c.631C>G

NM_001369586.1:c.634C>G

NM_003199.3:c.706C>G

NM_001243230.2:c.700C>G

Likely Benign

BP4 BS2

PS4 PM2 BS1

Evidence Links 0

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 3.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The highest population minor allele frequency of the p.Pro236Ala variant in TCF4 in gnomAD v4.1 is 0.00000062 in the European (non-Finnish) population (not sufficient to meet BS1 criteria). The p.Pro236Ala variant is observed in at least 2 unaffected individuals (Internal database - GeneDx, Internal database - Ambry) (BS2). Computational analysis prediction tools suggest that the p.Pro236Ala variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Pro236Ala variant in TCF4 is classified as a likely benign variant based on the ACMG/AMP criteria (BS2, BP4).

BP4

Computational analysis prediction tools suggest that the p.Pro236Ala variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4).

BS2

The p.Pro236Ala variant is observed in at least 2 unaffected individuals (Internal database - GeneDx, Internal database - Ambry) (BS2).

PS4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS1

The highest population minor allele frequency of the p.Pro236Ala variant in TCF4 in gnomAD v4.1 is 0.00000062 in the European (non-Finnish) population (not sufficient to meet BS1 criteria).

Curation History

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