NM_002834.5(PTPN11):c.1471C>T (p.Pro491Ser) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Jul 11, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000254684.34

Allele description [Variation Report for NM_002834.5(PTPN11):c.1471C>T (p.Pro491Ser)]

NM_002834.5(PTPN11):c.1471C>T (p.Pro491Ser)

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.1471C>T (p.Pro491Ser)

Other names:

p.P491S:CCC>TCC

HGVS:

NC_000012.12:g.112489047C>T
NG_007459.1:g.75316C>T
NM_001330437.2:c.1483C>T
NM_001374625.1:c.1468C>T
NM_002834.5:c.1471C>TMANE SELECT
NP_001317366.1:p.Pro495Ser
NP_001317366.1:p.Pro495Ser
NP_001361554.1:p.Pro490Ser
NP_002825.3:p.Pro491Ser
NP_002825.3:p.Pro491Ser
LRG_614t1:c.1471C>T
LRG_614:g.75316C>T
NC_000012.11:g.112926851C>T
NM_001330437.1:c.1483C>T
NM_002834.3:c.1471C>T
NM_002834.4:c.1471C>T
c.1471C>T

Protein change:

P490S

Links:

dbSNP: rs397507539

NCBI 1000 Genomes Browser:

rs397507539

Molecular consequence:

NM_001330437.2:c.1483C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.1468C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.1471C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000057441	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jul 11, 2022)	germline	clinical testing	Citation Link,
SCV001247469	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Dec 1, 2021)	germline	clinical testing	Citation Link,
SCV002501600	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 27, 2021)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 15001945, 31560489, 24891296, 24803665, 27521173, 30541462, 25741868
SCV002770732	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Dec 16, 2021)	unknown	clinical testing	PubMed (19) [See all records that cite these PMIDs] 18080325, 17020470, 16358218, 14982869, 31560489, 24891296, 30541462, 24803665, 27521173, 20543023, 20186801, 23996481, 34143244, 33568805, 28748642, 26607044, 22465605, 19077116, 26467025

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotype-phenotype correlations in Noonan syndrome.

Zenker M, Buheitel G, Rauch R, Koenig R, Bosse K, Kress W, Tietze HU, Doerr HG, Hofbeck M, Singer H, Reis A, Rauch A.

J Pediatr. 2004 Mar;144(3):368-74.

PubMed [citation]

PMID:: 15001945

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

See all PubMed Citations (21)

Details of each submission

From GeneDx, SCV000057441.16

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate this variant results in increased phosphatase activity of the SHP-2 protein (Edwards et al., 2014).; The majority of missense variants in this gene are considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 14982869, 24891296, 24803665, 27521173, 17020470, 28746941, 15985475, 19077116, 22465605, 30541462, 31560489, 29493581, 16358218, 15001945, 32737134, 27535533)

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

From CeGaT Center for Human Genetics Tuebingen, SCV001247469.24

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From AiLife Diagnostics, AiLife Diagnostics, SCV002501600.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (7)

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

From Athena Diagnostics, SCV002770732.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (19)

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

Last Updated: Sep 16, 2024

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