NM_002834.5(PTPN11):c.209A>G (p.Lys70Arg) AND Noonan syndrome 1

Germline classification:: Pathogenic (1 submission)
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:: RCV003313932.1

Allele description [Variation Report for NM_002834.5(PTPN11):c.209A>G (p.Lys70Arg)]

NM_002834.5(PTPN11):c.209A>G (p.Lys70Arg)

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.209A>G (p.Lys70Arg)

HGVS:

NC_000012.12:g.112450389A>G
NG_007459.1:g.36658A>G
NM_001330437.2:c.209A>G
NM_001374625.1:c.206A>G
NM_002834.5:c.209A>GMANE SELECT
NM_080601.3:c.209A>G
NP_001317366.1:p.Lys70Arg
NP_001361554.1:p.Lys69Arg
NP_002825.3:p.Lys70Arg
NP_542168.1:p.Lys70Arg
LRG_614t1:c.209A>G
LRG_614:g.36658A>G
NC_000012.11:g.112888193A>G
NM_002834.3:c.209A>G
NM_002834.4:c.209A>G
NM_002834.5(PTPN11):c.209A>GMANE SELECT
c.209A>G

Protein change:

K69R

Links:

dbSNP: rs397516801

NCBI 1000 Genomes Browser:

rs397516801

Molecular consequence:

NM_001330437.2:c.209A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.206A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.209A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.209A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Noonan syndrome 1 (NS1)
Synonyms:: Turner Syndrome, Male; Turner phenotype with normal karyotype; Female pseudo-Turner syndrome
Identifiers:: MONDO: MONDO:0008104; MedGen: C4551602; Orphanet: 648; OMIM: 163950

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004013556	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29084544, 29493581, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004013556

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

unknown

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	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders.

Xu S, Fan Y, Sun Y, Wang L, Gu X, Yu Y.

BMC Med Genomics. 2017 Oct 30;10(1):62. doi: 10.1186/s12920-017-0298-6.

PubMed [citation]

PMID:: 29084544
PMCID:: PMC5663114

ClinGen's RASopathy Expert Panel consensus methods for variant interpretation.

Gelb BD, Cavé H, Dillon MW, Gripp KW, Lee JA, Mason-Suares H, Rauen KA, Williams B, Zenker M, Vincent LM; ClinGen RASopathy Working Group..

Genet Med. 2018 Nov;20(11):1334-1345. doi: 10.1038/gim.2018.3. Epub 2018 Mar 1.

PubMed [citation]

PMID:: 29493581
PMCID:: PMC6119537

See all PubMed Citations (3)

Details of each submission

From 3billion, SCV004013556.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.67; 3Cnet: 0.73). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000044603 / PMID: 29084544). The variant has been previously reported as assumed (i.e. paternity and maternity not confirmed) de novo in at least one similarly affected unrelated individual (PMID: 29084544). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Oct 8, 2024

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