NM_002834.5(PTPN11):c.217A>C (p.Thr73Pro) AND Noonan syndrome 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 23, 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:: RCV003152671.1

Allele description [Variation Report for NM_002834.5(PTPN11):c.217A>C (p.Thr73Pro)]

NM_002834.5(PTPN11):c.217A>C (p.Thr73Pro)

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.217A>C (p.Thr73Pro)

Other names:

p.T73P:ACT>CCT

HGVS:

NC_000012.12:g.112450397A>C
NG_007459.1:g.36666A>C
NM_001330437.2:c.217A>C
NM_001374625.1:c.214A>C
NM_002834.5:c.217A>CMANE SELECT
NM_080601.3:c.217A>C
NP_001317366.1:p.Thr73Pro
NP_001361554.1:p.Thr72Pro
NP_002825.3:p.Thr73Pro
NP_542168.1:p.Thr73Pro
LRG_614t1:c.217A>C
LRG_614:g.36666A>C
NC_000012.11:g.112888201A>C
NM_002834.3:c.217A>C

Protein change:

T72P

Links:

dbSNP: rs397507513

NCBI 1000 Genomes Browser:

rs397507513

Molecular consequence:

NM_001330437.2:c.217A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.214A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.217A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.217A>C - 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
SCV003841675	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 23, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29493581, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003841675

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 23, 2023)

unknown

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

Citations

PubMed

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

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 3billion, SCV003841675.1

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

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: 0.97; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change (ClinVar ID: VCV000040501) and different missense changes at the same codon (p.Thr73Ile, p.Thr73Leu / ClinVar ID: VCV000013334, VCV000044604) have been previously reported as pathogenic/likely pathogenic with strong evidence. 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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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