NM_004380.3(CREBBP):c.5549T>C (p.Leu1850Pro) AND Rubinstein-Taybi syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 30, 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:: RCV003759599.2

Allele description [Variation Report for NM_004380.3(CREBBP):c.5549T>C (p.Leu1850Pro)]

NM_004380.3(CREBBP):c.5549T>C (p.Leu1850Pro)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_004380.3(CREBBP):c.5549T>C (p.Leu1850Pro)

HGVS:

NC_000016.10:g.3729498A>G
NG_009873.2:g.156216T>C
NM_001079846.1:c.5435T>C
NM_004380.3:c.5549T>CMANE SELECT
NP_001073315.1:p.Leu1812Pro
NP_004371.2:p.Leu1850Pro
LRG_1426t1:c.5549T>C
LRG_1426:g.156216T>C
LRG_1426p1:p.Leu1850Pro
NC_000016.9:g.3779499A>G

Protein change:

L1812P

Molecular consequence:

NM_001079846.1:c.5435T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004380.3:c.5549T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004507089	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 30, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27899157, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004507089

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 30, 2023)

germline

clinical testing

PubMed (2)
[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

Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort.

Eggers S, Sadedin S, van den Bergen JA, Robevska G, Ohnesorg T, Hewitt J, Lambeth L, Bouty A, Knarston IM, Tan TY, Cameron F, Werther G, Hutson J, O'Connell M, Grover SR, Heloury Y, Zacharin M, Bergman P, Kimber C, Brown J, Webb N, Hunter MF, et al.

Genome Biol. 2016 Nov 29;17(1):243.

PubMed [citation]

PMID:: 27899157
PMCID:: PMC5126855

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004507089.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CREBBP protein function. This variant is also known as p.L1812P. This missense change has been observed in individual(s) with clinical features of CREBBP-related conditions (PMID: 27899157). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1850 of the CREBBP protein (p.Leu1850Pro).

#	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

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