NM_001429.4(EP300):c.4783T>G (p.Phe1595Val) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Aug 31, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000414599.7

Allele description [Variation Report for NM_001429.4(EP300):c.4783T>G (p.Phe1595Val)]

NM_001429.4(EP300):c.4783T>G (p.Phe1595Val)

Gene:

EP300:E1A binding protein p300 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.2

Genomic location:

Preferred name:

NM_001429.4(EP300):c.4783T>G (p.Phe1595Val)

HGVS:

NC_000022.11:g.41176250T>G
NG_009817.1:g.88641T>G
NM_001362843.2:c.4705T>G
NM_001429.4:c.4783T>GMANE SELECT
NP_001349772.1:p.Phe1569Val
NP_001420.2:p.Phe1595Val
LRG_1422t1:c.4783T>G
LRG_1422:g.88641T>G
LRG_1422p1:p.Phe1595Val
NC_000022.10:g.41572254T>G
NM_001429.3:c.4783T>G

Protein change:

F1569V; PHE1595VAL

Links:

OMIM: 602700.0010; dbSNP: rs1057517732

NCBI 1000 Genomes Browser:

rs1057517732

Molecular consequence:

NM_001362843.2:c.4705T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001429.4:c.4783T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000490524	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Dec 9, 2016)	germline	clinical testing	Citation Link,
SCV001978549	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV001979660	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV002022186	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 31, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000490524.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

A pathogenic variant has been identified in the EP300 gene. The F1595V variant has been identified as a de novo variant with confirmed parentage in multiple unrelated individuals with developmental delay and dysmorphic features who were previously tested at GeneDx. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The F1595V variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts the F1595V variant is probably damaging to the protein structure/function. Therefore, the presence of this pathogenic variant is consistent with a diagnosis of Rubinstein-Taybi syndrome

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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001978549.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001979660.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Revvity Omics, Revvity, SCV002022186.3

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

#	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: Mar 16, 2024

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