NM_004380.3(CREBBP):c.4457_4458del (p.Cys1486fs) AND Rubinstein-Taybi syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 2, 2023
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:: RCV003593625.2

Allele description [Variation Report for NM_004380.3(CREBBP):c.4457_4458del (p.Cys1486fs)]

NM_004380.3(CREBBP):c.4457_4458del (p.Cys1486fs)

Gene:

CREBBP:CREB binding protein [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_004380.3(CREBBP):c.4457_4458del (p.Cys1486fs)

HGVS:

NC_000016.10:g.3736752_3736753del
NG_009873.2:g.148961_148962del
NG_132889.1:g.95_96del
NM_001079846.1:c.4343_4344del
NM_004380.3:c.4457_4458delMANE SELECT
NP_001073315.1:p.Cys1448fs
NP_004371.2:p.Cys1486fs
LRG_1426t1:c.4457_4458del
LRG_1426:g.148961_148962del
LRG_1426p1:p.Cys1486fs
NC_000016.9:g.3786753_3786754del

Protein change:

C1448fs

Molecular consequence:

NM_001079846.1:c.4343_4344del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004380.3:c.4457_4458del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Rubinstein-Taybi syndrome (RSTS)
Synonyms:: Broad thumb-hallux syndrome
Identifiers:: MONDO: MONDO:0019188; MedGen: C0035934; OMIM: PS180849

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004310296	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 2, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17052327, 18792986, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004310296

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 2, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Rubinstein-Taybi Syndrome: spectrum of CREBBP mutations in Italian patients.

Bentivegna A, Milani D, Gervasini C, Castronovo P, Mottadelli F, Manzini S, Colapietro P, Giordano L, Atzeri F, Divizia MT, Uzielli ML, Neri G, Bedeschi MF, Faravelli F, Selicorni A, Larizza L.

BMC Med Genet. 2006 Oct 19;7:77.

PubMed [citation]

PMID:: 17052327
PMCID:: PMC1626071

Genotype-phenotype correlations in Rubinstein-Taybi syndrome.

Schorry EK, Keddache M, Lanphear N, Rubinstein JH, Srodulski S, Fletcher D, Blough-Pfau RI, Grabowski GA.

Am J Med Genet A. 2008 Oct 1;146A(19):2512-9. doi: 10.1002/ajmg.a.32424.

PubMed [citation]

PMID:: 18792986

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004310296.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Cys1486Serfs*4) in the CREBBP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CREBBP are known to be pathogenic (PMID: 17052327, 18792986). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with CREBBP-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine