NM_002834.5(PTPN11):c.178G>T (p.Gly60Cys) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 27, 2020
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:: RCV002408501.9

Allele description [Variation Report for NM_002834.5(PTPN11):c.178G>T (p.Gly60Cys)]

NM_002834.5(PTPN11):c.178G>T (p.Gly60Cys)

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.178G>T (p.Gly60Cys)

Other names:

p.G60C:GGT>TGT

HGVS:

NC_000012.12:g.112450358G>T
NG_007459.1:g.36627G>T
NM_001330437.2:c.178G>T
NM_001374625.1:c.175G>T
NM_002834.5:c.178G>TMANE SELECT
NM_080601.3:c.178G>T
NP_001317366.1:p.Gly60Cys
NP_001361554.1:p.Gly59Cys
NP_002825.3:p.Gly60Cys
NP_002825.3:p.Gly60Cys
NP_542168.1:p.Gly60Cys
LRG_614t1:c.178G>T
LRG_614:g.36627G>T
LRG_614p1:p.Gly60Cys
NC_000012.11:g.112888162G>T
NM_002834.3:c.178G>T

Protein change:

G59C

Links:

dbSNP: rs397507507

NCBI 1000 Genomes Browser:

rs397507507

Molecular consequence:

NM_001330437.2:c.178G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.175G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.178G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.178G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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gi|1952754503|ref|XM_022415252.2|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002717198	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Mar 27, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16263833, 17301821, 18470943 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002717198

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Mar 27, 2020)

germline

clinical testing

PubMed (3)
[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

Noonan syndrome: relationships between genotype, growth, and growth factors.

Limal JM, Parfait B, Cabrol S, Bonnet D, Leheup B, Lyonnet S, Vidaud M, Le Bouc Y.

J Clin Endocrinol Metab. 2006 Jan;91(1):300-6. Epub 2005 Nov 1.

PubMed [citation]

PMID:: 16263833

A new NDE1/PDGFRB fusion transcript underlying chronic myelomonocytic leukaemia in Noonan Syndrome.

La Starza R, Rosati R, Roti G, Gorello P, Bardi A, Crescenzi B, Pierini V, Calabrese O, Baens M, Folens C, Cools J, Marynen P, Martelli MF, Mecucci C, Cuneo A.

Leukemia. 2007 Apr;21(4):830-3. Epub 2007 Feb 15. No abstract available.

PubMed [citation]

PMID:: 17301821

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002717198.2

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

Description

The p.G60C variant (also known as c.178G>T), located in coding exon 3 of the PTPN11 gene, results from a G to T substitution at nucleotide position 178. The glycine at codon 60 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was reported in one individual with Noonan syndrome, severe pulmonary valve stenosis, and chronic myelomonocytic leukaemia (La Starza R et al. Leukemia, 2007 Apr;21:830-3). It was also identified in an individual undergoing growth hormone treatment; however, clinical details were limited (Limal JM et al. J. Clin. Endocrinol. Metab., 2006 Jan;91:300-6). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. A known disease-causing mutation, p.G60A, has been described in the same codon (Tartaglia M et al. Am. J. Hum. Genet., 2002 Jun;70:1555-63; Tartaglia M et al. Am. J. Hum. Genet., 2006 Feb;78:279-90; Bertola DR et al. Genet. Test., 2006;10:186-91; Jongmans MC et al. Eur. J. Hum. Genet., 2011 Aug;19:870-4; Atik T et al. Indian J Pediatr, 2016 Jun;83:517-21). Based on the majority of available evidence to date, the p.G60C variant is likely to be pathogenic.

#	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 3, 2024

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