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

Variant: NM_001083962.2(TCF4):c.990G>A (p.Ser330=)

CA272714

160092 (ClinVar)

Gene: TCF4
Condition: Pitt-Hopkins syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 919996d2-6306-4345-9cff-1b4b6bd7694d
Approved on: 2024-02-23
Published on: 2024-03-31

HGVS expressions

NM_001083962.2:c.990G>A
NM_001083962.2(TCF4):c.990G>A (p.Ser330=)
NC_000018.10:g.55261466C>T
CM000680.2:g.55261466C>T
NC_000018.9:g.52928697C>T
CM000680.1:g.52928697C>T
NC_000018.8:g.51079695C>T
NG_011716.1:g.332164G>A
NG_011716.2:g.379528G>A
ENST00000354452.8:c.990G>A
ENST00000630720.3:c.510G>A
ENST00000635822.2:c.990G>A
ENST00000635990.2:n.670G>A
ENST00000636400.2:c.918G>A
ENST00000636751.2:c.*698G>A
ENST00000636822.2:c.600G>A
ENST00000637115.2:c.*880G>A
ENST00000637169.2:c.342G>A
ENST00000637239.2:n.1057G>A
ENST00000637250.2:n.684G>A
ENST00000637923.2:c.588G>A
ENST00000638154.3:c.1020G>A
ENST00000643689.1:c.600G>A
ENST00000674764.1:c.*601G>A
ENST00000675707.1:c.600G>A
ENST00000354452.7:c.990G>A
ENST00000356073.8:c.990G>A
ENST00000398339.5:c.1296G>A
ENST00000457482.7:c.510G>A
ENST00000537578.5:c.918G>A
ENST00000537856.7:c.600G>A
ENST00000540999.5:c.918G>A
ENST00000543082.5:c.864G>A
ENST00000544241.6:c.777G>A
ENST00000561831.7:c.510G>A
ENST00000561992.5:c.600G>A
ENST00000562680.5:n.1081G>A
ENST00000563760.5:n.582G>A
ENST00000564228.5:c.777G>A
ENST00000564403.6:c.1008G>A
ENST00000564999.5:c.990G>A
ENST00000565018.6:c.738G>A
ENST00000566279.5:c.810G>A
ENST00000566286.5:c.984G>A
ENST00000567880.5:c.810G>A
ENST00000568673.5:c.918G>A
ENST00000568740.5:c.915G>A
ENST00000570146.3:c.254G>A
ENST00000570177.6:c.600G>A
ENST00000570287.6:c.510G>A
ENST00000616053.4:c.738G>A
ENST00000626584.2:c.342G>A
ENST00000627136.2:n.591G>A
ENST00000628078.2:c.600G>A
ENST00000628360.1:n.87G>A
ENST00000628636.2:c.600G>A
ENST00000628689.2:c.*133G>A
ENST00000629343.2:c.600G>A
ENST00000629387.2:c.990G>A
ENST00000630720.2:c.510G>A
NM_001083962.1:c.990G>A
NM_001243226.2:c.1296G>A
NM_001243227.1:c.918G>A
NM_001243228.1:c.1008G>A
NM_001243230.1:c.984G>A
NM_001243231.1:c.864G>A
NM_001243232.1:c.777G>A
NM_001243233.1:c.600G>A
NM_001243234.1:c.510G>A
NM_001243235.1:c.510G>A
NM_001243236.1:c.510G>A
NM_001306207.1:c.918G>A
NM_001306208.1:c.777G>A
NM_003199.2:c.990G>A
NM_001330604.2:c.990G>A
NM_001330605.2:c.600G>A
NM_001348211.1:c.864G>A
NM_001348212.1:c.600G>A
NM_001348213.1:c.600G>A
NM_001348214.1:c.510G>A
NM_001348215.1:c.342G>A
NM_001348216.1:c.510G>A
NM_001348217.1:c.918G>A
NM_001348218.1:c.918G>A
NM_001348219.1:c.918G>A
NM_001348220.1:c.915G>A
NM_001243226.3:c.1296G>A
NM_001243227.2:c.918G>A
NM_001243228.2:c.1008G>A
NM_001243231.2:c.864G>A
NM_001243233.2:c.600G>A
NM_001243234.2:c.510G>A
NM_001243235.2:c.510G>A
NM_001243236.2:c.510G>A
NM_001330604.3:c.990G>A
NM_001330605.3:c.600G>A
NM_001348211.2:c.864G>A
NM_001348212.2:c.600G>A
NM_001348213.2:c.600G>A
NM_001348214.2:c.510G>A
NM_001348215.2:c.342G>A
NM_001348216.2:c.510G>A
NM_001348218.2:c.918G>A
NM_001348219.2:c.918G>A
NM_001369567.1:c.990G>A
NM_001369568.1:c.990G>A
NM_001369569.1:c.987G>A
NM_001369570.1:c.987G>A
NM_001369571.1:c.990G>A
NM_001369572.1:c.990G>A
NM_001369573.1:c.987G>A
NM_001369574.1:c.990G>A
NM_001369575.1:c.918G>A
NM_001369576.1:c.915G>A
NM_001369577.1:c.918G>A
NM_001369578.1:c.915G>A
NM_001369579.1:c.918G>A
NM_001369580.1:c.918G>A
NM_001369581.1:c.915G>A
NM_001369582.1:c.918G>A
NM_001369583.1:c.918G>A
NM_001369584.1:c.915G>A
NM_001369585.1:c.915G>A
NM_001369586.1:c.918G>A
NM_003199.3:c.990G>A
NM_001243230.2:c.984G>A
More

Pathogenic

Met criteria codes 5
PS4_Supporting PP3 PM6 PM2_Supporting PS2_Very Strong

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.Ser330= variant in TCF4 is absent from gnomAD v4 (PM2_supporting). Splice prediction analysis using multiple computational tools suggests an impact to splicing (PP3). The p.Ser330= variant has been observed in at least 2 individuals with intellectual disability/autism (PMIDs: 29695756, 25693842) (PS4_supporting). The p.Ser330= variant in TCF4 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with intellectual disability (PMID: 25693842, internal database -Invitae) (PM6). The p.Ser330= variant in TCF4 has been reported as a de novo occurrence (biological parentage confirmed) in at least 3 individuals with intellectual disability/autism (PMIDs: 29695756, 29158550, 31785789, 1981491, 33767182, internal database - Invitae) (PS2_very strong). In summary, the p.Ser330= variant in TCF4 is classified as pathogenic for Pitt-Hopkins syndrome based on the ACMG/AMP criteria (PM2_supporting, PP3, PS4_supporting, PM6, PS2_very strong).
Met criteria codes
PS4_Supporting
The p.Ser330= variant has been observed in at least 2 individuals with intellectual disability/autism (PMIDs: 29695756, 25693842) (PS4_supporting).
PP3
Splice prediction analysis using multiple computational tools suggests an impact to splicing (PP3).
PM6
The p.Ser330= variant in TCF4 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with intellectual disability (PMID: 25693842, internal database -Invitae) (PM6).
PM2_Supporting
The p.Ser330= variant in TCF4 is absent from gnomAD v4 (PM2_supporting).
PS2_Very Strong
The p.Ser330= variant in TCF4 has been reported as a de novo occurrence (biological parentage confirmed) in at least 3 individuals with intellectual disability/autism (PMIDs: 29695756, 29158550, 31785789, 31981491, 33767182, internal database -Invitae) (PS2_very strong).
Curation History
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