ClinVar Genomic variation as it relates to human health
NM_002834.5(PTPN11):c.172A>G (p.Asn58Asp)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_002834.5(PTPN11):c.172A>G (p.Asn58Asp)
Variation ID: 40487 Accession: VCV000040487.38
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 12q24.13 12: 112450352 (GRCh38) [ NCBI UCSC ] 12: 112888156 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jan 31, 2015 Apr 15, 2024 Dec 1, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002834.5:c.172A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002825.3:p.Asn58Asp missense NM_001330437.2:c.172A>G NP_001317366.1:p.Asn58Asp missense NM_001374625.1:c.169A>G NP_001361554.1:p.Asn57Asp missense NM_002834.4:c.172A>G NM_080601.3:c.172A>G NP_542168.1:p.Asn58Asp missense NC_000012.12:g.112450352A>G NC_000012.11:g.112888156A>G NG_007459.1:g.36621A>G LRG_614:g.36621A>G LRG_614t1:c.172A>G - Protein change
- N58D, N57D
- Other names
- p.N58D:AAC>GAC
- Canonical SPDI
- NC_000012.12:112450351:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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PTPN11 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
944 | 956 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Feb 25, 2022 | RCV000033455.15 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 20, 2014 | RCV000037627.6 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Aug 14, 2023 | RCV000234028.14 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 30, 2021 | RCV000768061.3 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Jul 24, 2023 | RCV001283812.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 3, 2021 | RCV001813242.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 9, 2017 | RCV002408493.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 24, 2023 | RCV003333001.1 | |
Pathogenic (1) |
criteria provided, single submitter
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May 24, 2023 | RCV003407390.4 | |
Pathogenic (1) |
criteria provided, single submitter
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- | RCV003335059.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 24, 2023 | RCV003333002.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 1, 2023 | RCV003991571.1 | |
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Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Oct 16, 2017)
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criteria provided, single submitter
Method: clinical testing
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Rasopathy
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918104.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: The PTPN11 c.172A>G (p.Asn58Asp) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant … (more)
Variant summary: The PTPN11 c.172A>G (p.Asn58Asp) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant has been reported in multiple patients with Noonan syndrome and is absent in 277532 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. (less)
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Pathogenic
(Mar 20, 2014)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000061289.6
First in ClinVar: May 03, 2013 Last updated: Jan 31, 2015 |
Comment:
The Asn58Asp variant in PTPN11 has previously been identified in >10 individuals with clinical features of Noonan syndrome, including at least 3 individuals whe re … (more)
The Asn58Asp variant in PTPN11 has previously been identified in >10 individuals with clinical features of Noonan syndrome, including at least 3 individuals whe re the variant was reported to have occurred de novo (Zenker 2004, Ferrero 2008, Ferreira 2005, Kitsiou-Tzeli 2006, Pierpont 2009, Tumurkhuu 2010, LMM unpublish ed data). This variant was not identified in large population studies. In summar y, this variant meets our criteria to be classified as pathogenic (http://pcpgm. partners.org/LMM). (less)
Number of individuals with the variant: 8
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Pathogenic
(Aug 12, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV002067360.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
Comment:
DNA sequence analysis of the PTPN11 gene demonstrated a sequence change, c.172A>G, in exon 3 that results in an amino acid change, p.Asn58Asp. This sequence … (more)
DNA sequence analysis of the PTPN11 gene demonstrated a sequence change, c.172A>G, in exon 3 that results in an amino acid change, p.Asn58Asp. This sequence change is not present in large population databases such as ExAC and gnomAD. The p.Asn58Asp change affects a moderately conserved amino acid residue located in a domain of the PTPN11 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Asn58Asp substitution. This variant has been reported in several individuals with a clinical diagnosis of Noonan syndrome, occurring de novo in at least 3 of these individuals (PMID:15001945, PMID:15956085, PMID:18678287, PMID:19077116, PMID:20030748, PMID:21590266). Furthermore, missense variants affecting the same amino acid residue (p.Asn58Lys and p.Asn58His) and nearby residues have also been reported in association with Noonan syndrome supporting the functional importance of protein domain (PMID: 12634870, PMID: 16263833). This sequence change is the likely cause of this phenotype, however functional studies have not been performed to prove this conclusively. (less)
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Pathogenic
(Aug 09, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002715650.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.N58D pathogenic mutation (also known as c.172A>G), located in coding exon 3 of the PTPN11 gene, results from an A to G substitution at … (more)
The p.N58D pathogenic mutation (also known as c.172A>G), located in coding exon 3 of the PTPN11 gene, results from an A to G substitution at nucleotide position 172. The asparagine at codon 58 is replaced by aspartic acid, an amino acid with highly similar properties. This alteration has been identified in numerous individuals with clinical features or a clinical diagnosis of Noonan Syndrome, including multiple de novo occurrences (Ezquieta B et al. Rev Esp Cardiol (Engl Ed), 2012 May;65:447-55; Choudhry KS et al. Mol. Genet. Metab., 2012 Jun;106:237-40; Stevenson DA et al. Clin. Genet., 2011 Dec;80:566-73; Pierpont EI et al. Genes Brain Behav., 2009 Apr;8:275-82; Ferrero GB et al. Eur J Med Genet 2008 Jul;51:566-72; Kitsiou-Tzeli S et al. Horm. Res., 2006 Jun;66:124-31; Ferreira LV et al. J. Clin. Endocrinol. Metab., 2005 Sep;90:5156-60; Zenker M et al. J. Pediatr., 2004 Mar;144:368-74). Two other alterations at the same amino acid position (p.N58K and p.N58H) have also been reported in patients with Noonan Syndrome. This variant is located in a mutation hotspot in the N-terminal Src homology 2 domain and is indicated to be structurally deleterious (Ambry internal data; Russo AA et al. Nature, 1998 Sep;395:237-43; Kannengiesser C et al. Hum. Mutat., 2009 Apr;30:564-74). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation (less)
Number of individuals with the variant: 1
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Pathogenic
(Feb 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000057360.15
First in ClinVar: Apr 04, 2013 Last updated: Mar 04, 2023 |
Comment:
The majority of missense variants in this gene are considered pathogenic (HGMD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious … (more)
The majority of missense variants in this gene are considered pathogenic (HGMD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19077116, 16804314, 32164556, 32059087, 19125092, 24803665, 15956085, 26918529, 15001945, 20030748, 18678287, 30693642, 30556322, 33144682, 33726816, 11992261, 16053901, 29493581, 9491886) (less)
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Pathogenic
(Jul 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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Metachondromatosis
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004041175.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
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Pathogenic
(Jul 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004041274.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
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Pathogenic
(Jul 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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LEOPARD syndrome 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004041375.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
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Pathogenic
(May 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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PTPN11-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004115769.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The PTPN11 c.172A>G variant is predicted to result in the amino acid substitution p.Asn58Asp. This variant has been reported in multiple individuals with Noonan syndrome … (more)
The PTPN11 c.172A>G variant is predicted to result in the amino acid substitution p.Asn58Asp. This variant has been reported in multiple individuals with Noonan syndrome including at least one report of it occurring de novo (see for example - Zenker et al. 2004. PubMed ID: 15001945; Kitsiou-Tzeli et al. 2006. PubMed ID: 16804314; Hakami et al. 2016. PubMed ID: 26918529). Additionally, different missense variants affecting this amino acid (p.Asn58His, p.Asn58Tyr, p.Asn58Ser, p.Asn58Lys) have been reported as pathogenic (Human Gene Mutation Database). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic. (less)
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Pathogenic
(May 20, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002019554.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Apr 26, 2021)
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criteria provided, single submitter
Method: research
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Noonan syndrome 1
Affected status: yes
Allele origin:
de novo
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HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: CSER-SouthSeq
Accession: SCV001736886.1 First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
Comment:
ACMG codes:PS2; PS4M; PM1; PP2; PP3; PP5
Number of individuals with the variant: 1
Clinical Features:
Posteriorly rotated ears (present) , Low-set ears (present) , Atrial septal defect (present) , Pulmonic stenosis (present) , Patent foramen ovale (present) , Abnormal helix … (more)
Posteriorly rotated ears (present) , Low-set ears (present) , Atrial septal defect (present) , Pulmonic stenosis (present) , Patent foramen ovale (present) , Abnormal helix morphology (present) (less)
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Pathogenic
(Feb 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome and Noonan-related syndrome
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002060728.1
First in ClinVar: Jan 20, 2022 Last updated: Jan 20, 2022 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome 1
Affected status: yes
Allele origin:
de novo
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Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille
Accession: SCV002559208.1
First in ClinVar: Aug 15, 2022 Last updated: Aug 15, 2022 |
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Pathogenic
(May 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome 1
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002761828.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
Comment:
The PTPN11 c.172A>G variant is a single nucleotide change in exon 3/16 of the PTPN11 gene, which is predicted to change the amino acid asparagine … (more)
The PTPN11 c.172A>G variant is a single nucleotide change in exon 3/16 of the PTPN11 gene, which is predicted to change the amino acid asparagine at position 58 in the protein to aspartic acid. This variant has been identified as a de novo variant in this fetus (PS2). The variant has been reported in 8 probands with a clinical presentation of Noonan Syndrome (e.g. PMID: 15001945; PMID: 16804314) (PS4). This variant is absent from population databases (PM2). This variant is a missense change at an amino acid residue where multiple different missense changes have been seen before in association with disease (e.g. PMID: 12634870) (PM5). Computational predictions support a deleterious effect on the gene or gene product (PP3). The variant has been reported in dbSNP (rs397507505) and in the HGMD database: CM044250. It has been reported as Pathogenic by other diagnostic laboratories (ClinVar Variation ID: 40487). (less)
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Pathogenic
(Feb 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome 1
Affected status: yes
Allele origin:
unknown
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3billion
Accession: SCV003842014.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. he variant is located in a mutational hot spot and/or well-established functional domain in which … (more)
The variant is not observed in the gnomAD v2.1.1 dataset. he 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: 0.76; 3Cnet: 0.98). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000040487). Different missense changes at the same codon (p.Asn58His, p.Asn58Lys, p.Asn58Tyr) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000040486, VCV000040488, VCV000040489, VCV000181494). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Short stature (present) , Abnormal facial shape (present) , Short neck (present) , Pectus carinatum (present) , Wide intermamillary distance (present) , Ventricular septal defect … (more)
Short stature (present) , Abnormal facial shape (present) , Short neck (present) , Pectus carinatum (present) , Wide intermamillary distance (present) , Ventricular septal defect (present) , Intellectual disability, mild (present) (less)
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Pathogenic
(Mar 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome 1
LEOPARD syndrome 1 Metachondromatosis Juvenile myelomonocytic leukemia
Affected status: unknown
Allele origin:
germline
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Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV000898915.2
First in ClinVar: Apr 25, 2019 Last updated: May 06, 2023 |
Comment:
PTPN11 NM_002834.4 exon 3 p.Asn58Asp (c.172A>G): This variant has been reported in the literature in at least 6 individuals with Noonan syndrome, occuring de novo … (more)
PTPN11 NM_002834.4 exon 3 p.Asn58Asp (c.172A>G): This variant has been reported in the literature in at least 6 individuals with Noonan syndrome, occuring de novo in at least 3 of these individuals (Zenker 2004 PMID:15001945, Ferreira 2005 PMID:15956085, Ferrero 2008 PMID:18678287, Pierpont 2009 PMID:19077116, Tumurkhuu 2010 PMID:20030748, Papadopolou 2012 PMID:21590266). This variant is not present in large control databases. This variant is present in ClinVar, with several labs classifying this variant as pathogenic (Variation ID:40487). Evolutionary conservation and computational predictive tools for this variant are unclear. Of note, this variant occurs within the N-SH2 domain, a critical region for the function of this gene, and increases the likelihood that this variant is damaging (Tartaglia 2002 PMID: 11992261, Strullu 2014 PMID:25097206). Furthermore, two other variants at this position (p.Asn58His and p.Asn58Lys) have also been reported in association with disease, supporting that this region has significance. In summary, this variant is classified as pathogenic. (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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PTPN11-Related Disorders
Affected status: yes
Allele origin:
germline
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Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV004046308.1
First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023 |
Comment:
This variant has been previously reported as a heterozygous change in patients with Noonan syndrome, including several individuals in whom the variant was reported as … (more)
This variant has been previously reported as a heterozygous change in patients with Noonan syndrome, including several individuals in whom the variant was reported as a de novo change (PMID: 19125092, 21590266, 15001945, 16804314, 15956085, 18678287, 19077116, 20030748, 32164556). This variant is in the N-SH2 domain, which is a hotspot domain for pathogenic variants associated with Noonan syndrome (PMID: 11992261). It is absent from the gnomAD population database and thus is presumed to be rare. In silico tools used to predict the effect of this variant on protein function yield discordant results. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.172A>G (p.Asn58Asp) variant is classified as Pathogenic. (less)
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Pathogenic
(Dec 01, 2023)
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criteria provided, single submitter
Method: research
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Male infertility with azoospermia or oligozoospermia due to single gene mutation
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Laan Lab, Human Genetics Research Group, University of Tartu
Accession: SCV004231710.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
Sex: male
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Pathogenic
(Aug 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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RASopathy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000287694.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, … (more)
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PTPN11 protein function. ClinVar contains an entry for this variant (Variation ID: 40487). This missense change has been observed in individual(s) with clinical features or diagnoses of Noonan syndrome (PMID: 15001945, 15956085, 16804314, 19077116, 19125092, 21590266). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 58 of the PTPN11 protein (p.Asn58Asp). (less)
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Pathogenic
(May 06, 2020)
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no assertion criteria provided
Method: clinical testing
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Noonan syndrome 1
Affected status: yes
Allele origin:
germline
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Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Accession: SCV001469214.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Undiagnosed RASopathies in infertile men. | Juchnewitsch AG | Frontiers in endocrinology | 2024 | DOI: 10.3389/fendo.2024.1312357 |
ClinGen's RASopathy Expert Panel consensus methods for variant interpretation. | Gelb BD | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29493581 |
Retrospective study of prenatal ultrasound findings in newborns with a Noonan spectrum disorder. | Hakami F | Prenatal diagnosis | 2016 | PMID: 26918529 |
Decreased bone mineralization in children with Noonan syndrome: another consequence of dysregulated RAS MAPKinase pathway? | Choudhry KS | Molecular genetics and metabolism | 2012 | PMID: 22551697 |
Alterations in RAS-MAPK genes in 200 Spanish patients with Noonan and other neuro-cardio-facio-cutaneous syndromes. Genotype and cardiopathy. | Ezquieta B | Revista espanola de cardiologia (English ed.) | 2012 | PMID: 22465605 |
Phenotypic spectrum of 80 Greek patients referred as Noonan syndrome and PTPN11 mutation analysis: the value of initial clinical assessment. | Papadopoulou A | European journal of pediatrics | 2012 | PMID: 21590266 |
Bone resorption in syndromes of the Ras/MAPK pathway. | Stevenson DA | Clinical genetics | 2011 | PMID: 21204800 |
Comprehensive genetic analysis of overlapping syndromes of RAS/RAF/MEK/ERK pathway. | Tumurkhuu M | Pediatrics international : official journal of the Japan Pediatric Society | 2010 | PMID: 20030748 |
Functional, structural, and genetic evaluation of 20 CDKN2A germ line mutations identified in melanoma-prone families or patients. | Kannengiesser C | Human mutation | 2009 | PMID: 19260062 |
Primary mixed glioneuronal tumor of the central nervous system in a patient with noonan syndrome: a case report and review of the literature. | Sherman CB | Journal of pediatric hematology/oncology | 2009 | PMID: 19125092 |
Genotype differences in cognitive functioning in Noonan syndrome. | Pierpont EI | Genes, brain, and behavior | 2009 | PMID: 19077116 |
Clinical and molecular characterization of 40 patients with Noonan syndrome. | Ferrero GB | European journal of medical genetics | 2008 | PMID: 18678287 |
Does the rare A172G mutation of PTPN11 gene convey a mild Noonan syndrome phenotype? | Kitsiou-Tzeli S | Hormone research | 2006 | PMID: 16804314 |
Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. | Tartaglia M | American journal of human genetics | 2006 | PMID: 16358218 |
PTPN11 (protein tyrosine phosphatase, nonreceptor type 11) mutations and response to growth hormone therapy in children with Noonan syndrome. | Ferreira LV | The Journal of clinical endocrinology and metabolism | 2005 | PMID: 15956085 |
Genotype-phenotype correlations in Noonan syndrome. | Zenker M | The Journal of pediatrics | 2004 | PMID: 15001945 |
Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndrome. | Musante L | European journal of human genetics : EJHG | 2003 | PMID: 12634870 |
Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a. | Russo AA | Nature | 1998 | PMID: 9751050 |
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Text-mined citations for rs397507505 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.