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.1965dupC (p.Gly656Argfs)

CA276982

212379 (ClinVar)

Gene: TCF4

Condition: Pitt-Hopkins syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 3fcdc732-4030-4866-83d7-9757bb69e914

Approved on: 2021-03-26

Published on: 2021-05-17

HGVS expressions

NM_001083962.1:c.1965dup

NM_001083962.1:c.1965dupC

NM_001083962.1(TCF4):c.1965dupC (p.Gly656Argfs)

ENST00000354452.8:c.1965dup

ENST00000635822.2:c.1845dup

ENST00000635990.2:n.1645dup

ENST00000636400.2:c.1893dup

ENST00000636751.2:c.*1673dup

ENST00000636822.2:c.1575dup

ENST00000637115.2:c.*1843dup

ENST00000637169.2:c.1317dup

ENST00000637239.2:n.2020dup

ENST00000637250.2:n.1659dup

ENST00000637923.2:n.1563dup

ENST00000638154.3:c.1992dup

ENST00000643689.1:c.1575dup

ENST00000674764.1:c.*1576dup

ENST00000675707.1:c.1575dup

ENST00000354452.7:c.1965dup

ENST00000356073.8:c.1953dup

ENST00000398339.5:c.2271dup

ENST00000457482.7:c.1485dup

ENST00000537578.5:c.1893dup

ENST00000537856.7:c.1563dup

ENST00000540999.5:c.1881dup

ENST00000543082.5:c.1827dup

ENST00000544241.6:c.1752dup

ENST00000561831.7:c.1473dup

ENST00000561992.5:c.1563dup

ENST00000562680.5:n.5488dup

ENST00000564228.5:n.1740dup

ENST00000564403.6:c.1983dup

ENST00000564999.5:c.1953dup

ENST00000565018.6:c.1701dup

ENST00000566279.5:c.1785dup

ENST00000566286.5:n.1944dup

ENST00000567880.5:n.1773dup

ENST00000568673.5:c.1893dup

ENST00000568740.5:c.1878dup

ENST00000570177.6:c.1563dup

ENST00000570287.6:c.1473dup

ENST00000616053.4:c.1701dup

ENST00000626466.1:n.988dup

ENST00000626584.2:c.1305dup

ENST00000626631.1:n.195dup

ENST00000629387.2:c.1965dup

NM_001243226.2:c.2271dup

NM_001243227.1:c.1893dup

NM_001243228.1:c.1983dup

NM_001243230.1:c.1944dup

NM_001243231.1:c.1827dup

NM_001243232.1:c.1752dup

NM_001243233.1:c.1563dup

NM_001243234.1:c.1485dup

NM_001243235.1:c.1473dup

NM_001243236.1:c.1473dup

NM_001306207.1:c.1881dup

NM_001306208.1:c.1740dup

NM_003199.2:c.1953dup

NM_001330604.2:c.1962dup

NM_001330605.2:c.1575dup

NM_001348211.1:c.1839dup

NM_001348212.1:c.1563dup

NM_001348213.1:c.1575dup

NM_001348214.1:c.1470dup

NM_001348215.1:c.1317dup

NM_001348216.1:c.1485dup

NM_001348217.1:c.1893dup

NM_001348218.1:c.1893dup

NM_001348219.1:c.1881dup

NM_001348220.1:c.1878dup

NM_001083962.2:c.1965dup

NM_001243226.3:c.2271dup

NM_001243227.2:c.1893dup

NM_001243228.2:c.1983dup

NM_001243231.2:c.1827dup

NM_001243233.2:c.1563dup

NM_001243234.2:c.1485dup

NM_001243235.2:c.1473dup

NM_001243236.2:c.1473dup

NM_001330604.3:c.1962dup

NM_001330605.3:c.1575dup

NM_001348211.2:c.1839dup

NM_001348212.2:c.1563dup

NM_001348213.2:c.1575dup

NM_001348214.2:c.1470dup

NM_001348215.2:c.1317dup

NM_001348216.2:c.1485dup

NM_001348218.2:c.1893dup

NM_001348219.2:c.1881dup

NM_001369567.1:c.1965dup

NM_001369568.1:c.1965dup

NM_001369569.1:c.1962dup

NM_001369570.1:c.1962dup

NM_001369571.1:c.1953dup

NM_001369572.1:c.1953dup

NM_001369573.1:c.1950dup

NM_001369574.1:c.1950dup

NM_001369575.1:c.1893dup

NM_001369576.1:c.1890dup

NM_001369577.1:c.1890dup

NM_001369578.1:c.1890dup

NM_001369579.1:c.1890dup

NM_001369580.1:c.1890dup

NM_001369581.1:c.1890dup

NM_001369582.1:c.1881dup

NM_001369583.1:c.1881dup

NM_001369584.1:c.1878dup

NM_001369585.1:c.1878dup

NM_001369586.1:c.1896dup

NM_003199.3:c.1953dup

NM_001243230.2:c.1944dup

NC_000018.10:g.55228277dup

CM000680.2:g.55228277dup

NC_000018.9:g.52895508dup

CM000680.1:g.52895508dup

NC_000018.8:g.51046506dup

NG_011716.1:g.365354dup

NG_011716.2:g.412718dup

Pathogenic

PVS1 PM2_Supporting PS2

Evidence Links 1

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.Gly656Argfs*55 variant in TCF4 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The p.Gly656Argfs*55 variant in TCF4 has been reported as a de novo occurrence (biological parentage confirmed) in an individual with Pitt-Hopkins syndrome (PMID 25326637) (PS2). This variant is absent from gnomAD (PM2_supporting). In summary, the p.Gly656Argfs*55 variant in TCF4 is classified as Pathogenic for Pitt-Hopkins syndrome based on the ACMG/AMP criteria (PVS1, PS2, PM2_supporting).

PVS1

The c.1965dupC variant in TCF4 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism.

PM2_Supporting

The c.1965dupC variant in TCF4 is absent from gnomAD.

PS2

The c.1965dupC variant in TCF4 has been reported as a confirmed de novo occurrence in an individual with developmental delay, hypotonia, peripheral hypertonia, leukodystrophy, white matter changes, optic atrophy, esotropia, monocular, myopia, and astigmatism (PMID 25326637).

The c.1965dupC variant in TCF4 has been reported as a confirmed de novo occurrence in a individual with developmental delay, hypotonia, peripheral hypertonia, leukodystrophy, white matter changes, optic atrophy, esotropia, monocular, myopia, and astigmatism. PubMed:25326637

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