NM_002834.5(PTPN11):c.1530G>C (p.Gln510His) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 28, 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:: RCV002399355.10

Allele description [Variation Report for NM_002834.5(PTPN11):c.1530G>C (p.Gln510His)]

NM_002834.5(PTPN11):c.1530G>C (p.Gln510His)

Gene:

PTPN11:protein tyrosine phosphatase non-receptor type 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.13

Genomic location:

Preferred name:

NM_002834.5(PTPN11):c.1530G>C (p.Gln510His)

Other names:

p.Q510H:CAG>CAC; NM_002834.4(PTPN11):c.1530G>C

HGVS:

NC_000012.12:g.112489106G>C
NG_007459.1:g.75375G>C
NM_001330437.2:c.1542G>C
NM_001374625.1:c.1527G>C
NM_002834.5:c.1530G>CMANE SELECT
NP_001317366.1:p.Gln514His
NP_001361554.1:p.Gln509His
NP_002825.3:p.Gln510His
NP_002825.3:p.Gln510His
LRG_614t1:c.1530G>C
LRG_614:g.75375G>C
LRG_614p1:p.Gln510His
NC_000012.11:g.112926910G>C
NM_002834.3:c.1530G>C
NM_002834.4:c.1530G>C

Protein change:

Q509H

Links:

dbSNP: rs397507550

NCBI 1000 Genomes Browser:

rs397507550

Molecular consequence:

NM_001330437.2:c.1542G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.1527G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.1530G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002705518	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 28, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 15520399, 15889278, 15948193, 16733669, 21910226, 27193571, 31040167, 31560489, 33318624 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002705518

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 28, 2023)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link

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

PTPN11 mutations in patients with LEOPARD syndrome: a French multicentric experience.

Keren B, Hadchouel A, Saba S, Sznajer Y, Bonneau D, Leheup B, Boute O, Gaillard D, Lacombe D, Layet V, Marlin S, Mortier G, Toutain A, Beylot C, Baumann C, Verloes A, Cavé H; French Collaborative Noonan Study Group.

J Med Genet. 2004 Nov;41(11):e117. No abstract available.

PubMed [citation]

PMID:: 15520399
PMCID:: PMC1735627

A novel mutation in the PTPN11 gene in a patient with Noonan syndrome and rapidly progressive hypertrophic cardiomyopathy.

Takahashi K, Kogaki S, Kurotobi S, Nasuno S, Ohta M, Okabe H, Wada K, Sakai N, Taniike M, Ozono K.

Eur J Pediatr. 2005 Aug;164(8):497-500. Epub 2005 May 12.

PubMed [citation]

PMID:: 15889278

See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV002705518.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The p.Q510H pathogenic mutation (also known as c.1530G>C), located in coding exon 13 of the PTPN11 gene, results from a G to C substitution at nucleotide position 1530. The glutamine at codon 510 is replaced by histidine, an amino acid with highly similar properties. This variant as been reported in multiple individuals with PTPN11-related RASopathy (Wakabayashi Y et al. Am. J. Med. Genet. A, 2011 Oct;155A:2529-33; Chinton J et al. Arch Argent Pediatr, 2019 Oct;117:330-337; Kauffman H et al. Pediatr Res, 2021 Aug;90:444-451). It has also been determined to be the result of a de novo mutation in a fetus with features including hydrops fetalis, pleural effusion, cardiomyopathy, and hepatomegaly (Stuurman KE et al. J Med Genet, 2019 Oct;56:654-661). Another variant at the same codon, c.1530G>T (p.Q510H), has been described previously in fetuses with cystic hygroma (Gezdirici A et al. J Matern Fetal Neonatal Med, 2017 Apr;30:938-941). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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: Nov 24, 2024

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