U.S. flag

An official website of the United States government

NM_001083962.2(TCF4):c.1733G>A (p.Arg578His) AND Inborn genetic diseases

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 12, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002515762.9

Allele description [Variation Report for NM_001083962.2(TCF4):c.1733G>A (p.Arg578His)]

NM_001083962.2(TCF4):c.1733G>A (p.Arg578His)

Gene:
TCF4:transcription factor 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q21.2
Genomic location:
Preferred name:
NM_001083962.2(TCF4):c.1733G>A (p.Arg578His)
Other names:
p.R578H:CGT>CAT
HGVS:
  • NC_000018.10:g.55228993C>T
  • NG_011716.2:g.412001G>A
  • NM_001083962.2:c.1733G>AMANE SELECT
  • NM_001243226.3:c.2039G>A
  • NM_001243227.2:c.1661G>A
  • NM_001243228.2:c.1751G>A
  • NM_001243230.2:c.1712G>A
  • NM_001243231.2:c.1595G>A
  • NM_001243232.1:c.1520G>A
  • NM_001243233.2:c.1331G>A
  • NM_001243234.2:c.1253G>A
  • NM_001243235.2:c.1241G>A
  • NM_001243236.2:c.1241G>A
  • NM_001306207.1:c.1649G>A
  • NM_001306208.1:c.1508G>A
  • NM_001330604.3:c.1730G>A
  • NM_001330605.3:c.1343G>A
  • NM_001348211.2:c.1607G>A
  • NM_001348212.2:c.1331G>A
  • NM_001348213.2:c.1343G>A
  • NM_001348214.2:c.1238G>A
  • NM_001348215.2:c.1085G>A
  • NM_001348216.2:c.1253G>A
  • NM_001348217.1:c.1661G>A
  • NM_001348218.2:c.1661G>A
  • NM_001348219.2:c.1649G>A
  • NM_001348220.1:c.1646G>A
  • NM_001369567.1:c.1733G>A
  • NM_001369568.1:c.1733G>A
  • NM_001369569.1:c.1730G>A
  • NM_001369570.1:c.1730G>A
  • NM_001369571.1:c.1721G>A
  • NM_001369572.1:c.1721G>A
  • NM_001369573.1:c.1718G>A
  • NM_001369574.1:c.1718G>A
  • NM_001369575.1:c.1661G>A
  • NM_001369576.1:c.1658G>A
  • NM_001369577.1:c.1658G>A
  • NM_001369578.1:c.1658G>A
  • NM_001369579.1:c.1658G>A
  • NM_001369580.1:c.1658G>A
  • NM_001369581.1:c.1658G>A
  • NM_001369582.1:c.1649G>A
  • NM_001369583.1:c.1649G>A
  • NM_001369584.1:c.1646G>A
  • NM_001369585.1:c.1646G>A
  • NM_001369586.1:c.1664G>A
  • NM_003199.2:c.1721G>A
  • NM_003199.3:c.1721G>A
  • NP_001077431.1:p.Arg578His
  • NP_001230155.2:p.Arg680His
  • NP_001230156.1:p.Arg554His
  • NP_001230157.1:p.Arg584His
  • NP_001230159.1:p.Arg571His
  • NP_001230160.1:p.Arg532His
  • NP_001230161.1:p.Arg507His
  • NP_001230162.1:p.Arg444His
  • NP_001230163.1:p.Arg418His
  • NP_001230164.1:p.Arg414His
  • NP_001230165.1:p.Arg414His
  • NP_001293136.1:p.Arg550His
  • NP_001293137.1:p.Arg503His
  • NP_001317533.1:p.Arg577His
  • NP_001317534.1:p.Arg448His
  • NP_001335140.1:p.Arg536His
  • NP_001335141.1:p.Arg444His
  • NP_001335142.1:p.Arg448His
  • NP_001335143.1:p.Arg413His
  • NP_001335144.1:p.Arg362His
  • NP_001335145.1:p.Arg418His
  • NP_001335146.1:p.Arg554His
  • NP_001335147.1:p.Arg554His
  • NP_001335148.1:p.Arg550His
  • NP_001335149.1:p.Arg549His
  • NP_001356496.1:p.Arg578His
  • NP_001356497.1:p.Arg578His
  • NP_001356498.1:p.Arg577His
  • NP_001356499.1:p.Arg577His
  • NP_001356500.1:p.Arg574His
  • NP_001356501.1:p.Arg574His
  • NP_001356502.1:p.Arg573His
  • NP_001356503.1:p.Arg573His
  • NP_001356504.1:p.Arg554His
  • NP_001356505.1:p.Arg553His
  • NP_001356506.1:p.Arg553His
  • NP_001356507.1:p.Arg553His
  • NP_001356508.1:p.Arg553His
  • NP_001356509.1:p.Arg553His
  • NP_001356510.1:p.Arg553His
  • NP_001356511.1:p.Arg550His
  • NP_001356512.1:p.Arg550His
  • NP_001356513.1:p.Arg549His
  • NP_001356514.1:p.Arg549His
  • NP_001356515.1:p.Arg555His
  • NP_003190.1:p.Arg574His
  • NC_000018.9:g.52896224C>T
  • NM_001083962.1:c.1733G>A
  • NM_001083962.2(TCF4):c.1733G>AMANE SELECT
  • NM_001243226.2:c.2039G>A
Protein change:
R362H
Links:
dbSNP: rs121909123
NCBI 1000 Genomes Browser:
rs121909123
Molecular consequence:
  • NM_001083962.2:c.1733G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243226.3:c.2039G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243227.2:c.1661G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243228.2:c.1751G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243230.2:c.1712G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243231.2:c.1595G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243232.1:c.1520G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243233.2:c.1331G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243234.2:c.1253G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243235.2:c.1241G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243236.2:c.1241G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001306207.1:c.1649G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001306208.1:c.1508G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330604.3:c.1730G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330605.3:c.1343G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001348211.2:c.1607G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001348212.2:c.1331G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001348213.2:c.1343G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001348214.2:c.1238G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001348215.2:c.1085G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001348216.2:c.1253G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001348217.1:c.1661G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001348218.2:c.1661G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001348219.2:c.1649G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001348220.1:c.1646G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369567.1:c.1733G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369568.1:c.1733G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369569.1:c.1730G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369570.1:c.1730G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369571.1:c.1721G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369572.1:c.1721G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369573.1:c.1718G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369574.1:c.1718G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369575.1:c.1661G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369576.1:c.1658G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369577.1:c.1658G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369578.1:c.1658G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369579.1:c.1658G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369580.1:c.1658G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369581.1:c.1658G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369582.1:c.1649G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369583.1:c.1649G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369584.1:c.1646G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369585.1:c.1646G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369586.1:c.1664G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003199.3:c.1721G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003564413Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Likely pathogenic
(Sep 12, 2022)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Further delineation of Pitt-Hopkins syndrome: phenotypic and genotypic description of 16 novel patients.

Zweier C, Sticht H, Bijlsma EK, Clayton-Smith J, Boonen SE, Fryer A, Greally MT, Hoffmann L, den Hollander NS, Jongmans M, Kant SG, King MD, Lynch SA, McKee S, Midro AT, Park SM, Ricotti V, Tarantino E, Wessels M, Peippo M, Rauch A.

J Med Genet. 2008 Nov;45(11):738-44. doi: 10.1136/jmg.2008.060129. Epub 2008 Aug 26.

PubMed [citation]
PMID:
18728071

The Pitt-Hopkins syndrome: report of 16 new patients and clinical diagnostic criteria.

Marangi G, Ricciardi S, Orteschi D, Lattante S, Murdolo M, Dallapiccola B, Biscione C, Lecce R, Chiurazzi P, Romano C, Greco D, Pettinato R, Sorge G, Pantaleoni C, Alfei E, Toldo I, Magnani C, Bonanni P, Martinez F, Serra G, Battaglia D, Lettori D, et al.

Am J Med Genet A. 2011 Jul;155A(7):1536-45. doi: 10.1002/ajmg.a.34070. Epub 2011 Jun 10.

PubMed [citation]
PMID:
21671391
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV003564413.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

The c.1733G>A (p.R578H) alteration is located in exon 18 (coding exon 17) of the TCF4 gene. This alteration results from a G to A substitution at nucleotide position 1733, causing the arginine (R) at amino acid position 578 to be replaced by a histidine (H). Based on data from the Genome Aggregation Database (gnomAD), the TCF4 c.1733G>A alteration was not observed, with coverage at this position. This variant has been identified in several individuals with clinical features of Pitt-Hopkins syndrome (Zweier, 2008; Marangi, 2011; Whalen, 2012; Mary, 2018; Lindy, 2018). This variant completely abrogated DNA binding for homodimers and severely impaired DNA binding for heterodimers (Sepp, 2012). The p.R578H alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 15, 2024