ClinVar Genomic variation as it relates to human health
NM_002834.5(PTPN11):c.1381G>A (p.Ala461Thr)
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.1381G>A (p.Ala461Thr)
Variation ID: 13342 Accession: VCV000013342.40
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 12q24.13 12: 112488444 (GRCh38) [ NCBI UCSC ] 12: 112926248 (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 Oct 1, 2013 Sep 16, 2024 Sep 2, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002834.5:c.1381G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002825.3:p.Ala461Thr missense NM_001330437.2:c.1393G>A NP_001317366.1:p.Ala465Thr missense NM_001374625.1:c.1378G>A NP_001361554.1:p.Ala460Thr missense NC_000012.12:g.112488444G>A NC_000012.11:g.112926248G>A NG_007459.1:g.74713G>A LRG_614:g.74713G>A LRG_614t1:c.1381G>A - Protein change
- A461T, A465T, A460T
- Other names
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p.A461T:GCT>ACT
- Canonical SPDI
- NC_000012.12:112488443:G:A
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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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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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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 |
971 | 983 |
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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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 (2) |
criteria provided, multiple submitters, no conflicts
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Sep 6, 2022 | RCV000033530.10 | |
Pathogenic (3) |
no assertion criteria provided
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Nov 1, 2004 | RCV000055882.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 26, 2015 | RCV000037611.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 7, 2018 | RCV001002017.9 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 9, 2023 | RCV000529342.9 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Sep 2, 2024 | RCV001089941.8 | |
PTPN11-related disorder
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Pathogenic (1) |
criteria provided, single submitter
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Jan 18, 2023 | RCV004532345.1 |
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
(Feb 26, 2015)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome with multiple lentigines
(Autosomal dominant inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000061272.7
First in ClinVar: May 03, 2013 Last updated: May 29, 2016 |
Comment:
The p.Ala461Thr variant in PTPN11 has been previously identified in 10 individua ls with clinical features of a LEOPARD (Sarkozy 2004, Yoshida 2004, Digilio 2010 … (more)
The p.Ala461Thr variant in PTPN11 has been previously identified in 10 individua ls with clinical features of a LEOPARD (Sarkozy 2004, Yoshida 2004, Digilio 2010 , Chu 2013, LMM unpublished data) and occurred de novo in 3 of these individuals (Sarkozy 2004, Chu 2013, LMM unpublished data). It was absent from large popula tion studies. Furthermore, in-vitro and in-vivo functional studies suggest this variant has a dominant negative effect, which is an established pathogenic mecha nism in LEOPARD (Kontaridis 2006, Stewart 2010, Yu 2014). In summary, this varia nt meets our criteria to be classified as pathogenic for a LEOPARD (http://www.p artners.org/personalizedmedicine/LMM). (less)
Number of individuals with the variant: 6
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Pathogenic
(Aug 07, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001159835.1
First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020 |
Comment:
The PTPN11 c.1381G>A; p.Ala461Thr variant (rs121918468) is reported in the literature in multiple individuals affected with LEOPARD syndrome and symptoms of Noonan syndrome (Chu 2013, … (more)
The PTPN11 c.1381G>A; p.Ala461Thr variant (rs121918468) is reported in the literature in multiple individuals affected with LEOPARD syndrome and symptoms of Noonan syndrome (Chu 2013, Sarkozy 2004, Yoshida 2004). It is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 13342) and is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant occurs in the protein tyrosine signature motif involved in phosphate binding (Kontaridis 2006, Sarkozy 2004, Yu 2014), and other variants associated with LEOPARD syndrome, including another variant at the same codon, p.Ala461Ser, have also been described in this domain (Yoshida 2004, Osawa 2009). Biochemical characterization of p.Ala461Thr PTPN11 variant protein shows severely reduced phosphatase activity (Kontaridis 2006, Yu 2014). This variant also fails to rescue developmental defects of a zebrafish shp2 (PTPN11) morphant to the same extent as wildtype (Bonetti 2014, Stewart 2010). The alanine at codon 461 is highly conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on available information, the p.Ala461Thr variant is considered pathogenic. REFERENCES Bonetti M et al. Noonan and LEOPARD syndrome Shp2 variants induce heart displacement defects in zebrafish. Development. 2014 May;141(9):1961-70. Chu HS et al. Syndromic Hearing Loss in Association with PTPN11-Related Disorder: The Experience of Cochlear Implantation in a Child with LEOPARD Syndrome. Clin Exp Otorhinolaryngol. 2013 Jun;6(2):99-102. Kontaridis MI et al. PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. J Biol Chem. 2006 Mar 10;281(10):6785-92. Osawa R et al. A novel PTPN11 missense mutation in a patient with LEOPARD syndrome. Br J Dermatol. 2009 Nov;161(5):1202-4. Sarkozy A et al. A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome. Eur J Hum Genet. 2004 Dec;12(12):1069-72. Stewart RA et al. Phosphatase-dependent and -independent functions of Shp2 in neural crest cells underlie LEOPARD syndrome pathogenesis. Dev Cell. 2010 May 18;18(5):750-62. Yoshida R et al. Two novel and one recurrent PTPN11 mutations in LEOPARD syndrome. Am J Med Genet A. 2004 Nov 1;130A(4):432-4. Yu ZH et al. Molecular basis of gain-of-function LEOPARD syndrome-associated SHP2 mutations. Biochemistry. 2014 Jul 1;53(25):4136-51. (less)
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Pathogenic
(Oct 26, 2020)
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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: SCV000698054.2
First in ClinVar: Mar 17, 2018 Last updated: Nov 11, 2020 |
Comment:
Variant summary: PTPN11 c.1381G>A (p.Ala461Thr) results in a non-conservative amino acid change located in the PTP type protein phosphatase domain of the encoded protein sequence. … (more)
Variant summary: PTPN11 c.1381G>A (p.Ala461Thr) results in a non-conservative amino acid change located in the PTP type protein phosphatase domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251372 control chromosomes (gnomAD and publication data). c.1381G>A has been reported in the literature in multiple individuals with clinical features of NSRD, including de novo occurrences (Ypshida_2004, Chu_2011, Lee_2011, Digilio_2012, Ezquieta_2012, Croonen_2013, Leach_2019). These data indicate that the variant is very likely to be associated with disease. Functional studies report the variant effect results in catalytic inactivity and was shown to strongly inhibiting EGF-evoked Erk activation in a dominant-negative manner (Kontaridis_2006, Yu_2014). Four ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Feb 02, 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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Centro Nacional de Genética Medica "Dr. Eduardo E. Castilla", Administración Nacional de Laboratorios e Institutos de Salud
Accession: SCV002098084.1
First in ClinVar: Aug 29, 2022 Last updated: Aug 29, 2022 |
Clinical Features:
Asymmetric hypertrophic septal cardiomyopathy (present) , subaortic stenosis (present) , hypertelorism (present) , right cryptorchidism (present) , epicanthus (present) , low pinna implantation (present)
Sex: male
Tissue: blood
Secondary finding: no
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Pathogenic
(Sep 06, 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: SCV000057435.13
First in ClinVar: Apr 04, 2013 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate this variant results in either a dramatic reduction of catalytic activity or complete catalytic inactivity (Yu et al., 2014; Kontaridis et … (more)
Published functional studies demonstrate this variant results in either a dramatic reduction of catalytic activity or complete catalytic inactivity (Yu et al., 2014; Kontaridis et al., 2006); Missense variants in this gene are often considered pathogenic (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24935154, 20493809, 24718990, 16377799, 25937001, 24803665, 15470362, 28483241, 15389709, 23799168, 30055033, 30050098, 29907801, 32573669, 26918529, 24077912) (less)
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Pathogenic
(Jan 18, 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: SCV004114248.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The PTPN11 c.1381G>A variant is predicted to result in the amino acid substitution p.Ala461Thr. This variant has been documented in at least four individuals with … (more)
The PTPN11 c.1381G>A variant is predicted to result in the amino acid substitution p.Ala461Thr. This variant has been documented in at least four individuals with Noonan syndrome with multiple lentigines (Sarkozy et al. 2004. PubMed ID: 15470362; Yoshida et al. 2004. PubMed ID: 15389709; Chu et al. 2013. PubMed ID: 23799168; van Nierop et al. 2017. PubMed ID: 28483241) and was de novo in at least two of these individuals (Sarkozy et al. 2004. PubMed ID: 15470362; Chu et al. 2013. PubMed ID: 23799168). Additionally, this variant was found in three prenatal cases with cystic hygroma with or without congenital heart defects (Hakami et al. 2016. PubMed ID: 26918529; Table S2 - Leach et al. 2019. PubMed ID: 29907801). Two studies found the p.Ala461Thr variant imparts a dominant-negative effect resulting in a reduction in RAS pathway signaling (Kontaridis et al. 2006. PubMed ID: 16377799; Stewart et al. 2010. PubMed ID: 20493809). Consistent with the previous studies, another found the variant does result in lower catalytic activity; however, the activation of PTPN11 was prolonged (Yu et al. 2014. PubMed ID: 24935154). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant has been interpreted as pathogenic by multiple labs in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/13342/). This variant is interpreted as pathogenic. (less)
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Pathogenic
(Jan 09, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000659032.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PTPN11 function (PMID: 16377799, 20493809, 24718990, … (more)
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PTPN11 function (PMID: 16377799, 20493809, 24718990, 24935154). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is expected to disrupt PTPN11 function. ClinVar contains an entry for this variant (Variation ID: 13342). This missense change has been observed in individual(s) with LEOPARD syndrome (PMID: 15389709, 15470362, 23799168). 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 alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 461 of the PTPN11 protein (p.Ala461Thr). (less)
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Pathogenic
(Feb 02, 2022)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV001244985.3
First in ClinVar: May 04, 2020 Last updated: Jul 23, 2024 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as pathogenic. Following criteria are met: 0103 - Both loss- and gain-of-function are known mechanisms … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as pathogenic. Following criteria are met: 0103 - Both loss- and gain-of-function are known mechanisms of disease for this gene. Metachondromatosis (MIM#156250) and Noonan syndrome with multiple lentigines have been associated with loss of function variants, whereas Noonan syndrome 1 (MIM#163950) is caused by gain of function variants (PMIDs: 11992261, 24935154, 21533187). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene associated with Noonan syndrome are known to have variable expressivity (GeneReviews). 0200 - Variant is predicted to result in a missense amino acid change from alanine to threonine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0601 - Variant is located in the well-established functional protein-tyrosine phosphatase (PTP) domain. The alanine residue at position 461, is an active site involved in substrate binding in the PTP domain (UniProt, PMID 24935154). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in multiple individuals with Noonan syndrome and LEOPARD syndrome, several with de novo inheritance (PMID: 23799168, PMID: 15470362, PMID: 21784453, PMID: 22190897, VCGS, ClinVar). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Pathogenic
(Sep 02, 2024)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome 1
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004807422.2
First in ClinVar: Apr 06, 2024 Last updated: Sep 16, 2024 |
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Pathogenic
(Nov 01, 2004)
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no assertion criteria provided
Method: literature only
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LEOPARD SYNDROME 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000034519.3
First in ClinVar: Apr 04, 2013 Last updated: Aug 22, 2016 |
Comment on evidence:
In a Japanese patient with LEOPARD syndrome (LPRD1; 151100), Yoshida et al. (2004) identified heterozygosity for a 1381G-A transition in exon 12 of the PTPN11 … (more)
In a Japanese patient with LEOPARD syndrome (LPRD1; 151100), Yoshida et al. (2004) identified heterozygosity for a 1381G-A transition in exon 12 of the PTPN11 gene, resulting in an ala461-to-thr (A461T) substitution. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: research
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LEOPARD syndrome 1
Affected status: yes
Allele origin:
unknown
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Division of Human Genetics, National Health Laboratory Service/University of the Witwatersrand
Accession: SCV003840150.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Number of individuals with the variant: 1
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not provided
(-)
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no classification provided
Method: literature only
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LEOPARD syndrome 1
Affected status: not provided
Allele origin:
unknown
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GeneReviews
Accession: SCV000086888.2
First in ClinVar: Oct 01, 2013 Last updated: Oct 01, 2022 |
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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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Noonan Syndrome with Multiple Lentigines. | Adam MP | - | 2022 | PMID: 20301557 |
Comparative assessment of gene-specific variant distribution in prenatal and postnatal cohorts tested for Noonan syndrome and related conditions. | Leach NT | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 29907801 |
Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11. | van Nierop JWI | International journal of pediatric otorhinolaryngology | 2017 | PMID: 28483241 |
Genomic Classification and Prognosis in Acute Myeloid Leukemia. | Papaemmanuil E | The New England journal of medicine | 2016 | PMID: 27276561 |
The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. | Arber DA | Blood | 2016 | PMID: 27069254 |
Subclonal mutations in SETBP1 confer a poor prognosis in juvenile myelomonocytic leukemia. | Stieglitz E | Blood | 2015 | PMID: 25395418 |
Juvenile myelomonocytic leukaemia and Noonan syndrome. | Strullu M | Journal of medical genetics | 2014 | PMID: 25097206 |
Molecular basis of gain-of-function LEOPARD syndrome-associated SHP2 mutations. | Yu ZH | Biochemistry | 2014 | PMID: 24935154 |
Noonan and LEOPARD syndrome Shp2 variants induce heart displacement defects in zebrafish. | Bonetti M | Development (Cambridge, England) | 2014 | PMID: 24718990 |
Syndromic Hearing Loss in Association with PTPN11-Related Disorder: The Experience of Cochlear Implantation in a Child with LEOPARD Syndrome. | Chu HS | Clinical and experimental otorhinolaryngology | 2013 | PMID: 23799168 |
Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings. | Croonen EA | European journal of human genetics : EJHG | 2013 | PMID: 23321623 |
Atrioventricular canal defect in patients with RASopathies. | Digilio MC | European journal of human genetics : EJHG | 2013 | PMID: 22781091 |
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 |
RASopathies: Clinical Diagnosis in the First Year of Life. | Digilio MC | Molecular syndromology | 2011 | PMID: 22190897 |
Spectrum of mutations in Noonan syndrome and their correlation with phenotypes. | Lee BH | The Journal of pediatrics | 2011 | PMID: 21784453 |
Loss-of-function mutations in PTPN11 cause metachondromatosis, but not Ollier disease or Maffucci syndrome. | Bowen ME | PLoS genetics | 2011 | PMID: 21533187 |
Phosphatase-dependent and -independent functions of Shp2 in neural crest cells underlie LEOPARD syndrome pathogenesis. | Stewart RA | Developmental cell | 2010 | PMID: 20493809 |
Correlation of clinical features with the mutational status of GM-CSF signaling pathway-related genes in juvenile myelomonocytic leukemia. | Yoshida N | Pediatric research | 2009 | PMID: 19047918 |
Characterization of acute myeloid leukemia with PTPN11 mutation: the mutation is closely associated with NPM1 mutation but inversely related to FLT3/ITD. | Hou HA | Leukemia | 2008 | PMID: 17972951 |
PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. | Kontaridis MI | The Journal of biological chemistry | 2006 | PMID: 16377799 |
Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations. | Mohi MG | Cancer cell | 2005 | PMID: 15710330 |
A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome. | Sarkozy A | European journal of human genetics : EJHG | 2004 | PMID: 15470362 |
Two novel and one recurrent PTPN11 mutations in LEOPARD syndrome. | Yoshida R | American journal of medical genetics. Part A | 2004 | PMID: 15389709 |
PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children's Cancer Group. | Loh ML | Leukemia | 2004 | PMID: 15385933 |
Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis. | Loh ML | Blood | 2004 | PMID: 14644997 |
PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. | Tartaglia M | American journal of human genetics | 2002 | PMID: 11992261 |
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Text-mined citations for rs121918468 ...
HelpRecord last updated Nov 10, 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.