NM_002834.5(PTPN11):c.762ACA[2] (p.Gln257del) AND RASopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 20, 2025
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:: RCV002549756.5

Allele description [Variation Report for NM_002834.5(PTPN11):c.762ACA[2] (p.Gln257del)]

NM_002834.5(PTPN11):c.762ACA[2] (p.Gln257del)

Gene:

PTPN11:protein tyrosine phosphatase non-receptor type 11 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

12q24.13

Genomic location:

Preferred name:

NM_002834.5(PTPN11):c.762ACA[2] (p.Gln257del)

HGVS:

NC_000012.12:g.112472949ACA[2]
NC_000012.12:g.112472949_112472951ACA[2]
NG_007459.1:g.59218ACA[2]
NM_001330437.2:c.762ACA[2]
NM_001374625.1:c.759ACA[2]
NM_002834.3:c.768_770del
NM_002834.5:c.762ACA[2]MANE SELECT
NM_080601.3:c.762ACA[2]
NP_001317366.1:p.Gln257del
NP_001361554.1:p.Gln256del
NP_002825.3:p.Gln257del
NP_542168.1:p.Gln257del
LRG_614t1:c.768_770del
LRG_614:g.59218ACA[2]
NC_000012.11:g.112910753ACA[2]
NC_000012.11:g.112910753_112910755del
NM_002834.4:c.768_770delACA
NM_002834.5:c.768_770delMANE SELECT

Protein change:

Q256del

Links:

dbSNP: rs397507524

Molecular consequence:

NM_001330437.2:c.762ACA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001374625.1:c.759ACA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_002834.5:c.762ACA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_080601.3:c.762ACA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: RASopathy
Synonyms:: rasopathies; Noonan spectrum disorder
Identifiers:: MONDO: MONDO:0021060; MedGen: C5555857

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002938004	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 20, 2025)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32112654, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002938004

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 20, 2025)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Pathogenic PTPN11 variants involving the poly-glutamine Gln(255) -Gln(256) -Gln(257) stretch highlight the relevance of helix B in SHP2's functional regulation.

Martinelli S, Pannone L, Lissewski C, Brinkmann J, Flex E, Schanze D, Calligari P, Anselmi M, Pantaleoni F, Canale VC, Radio FC, Ioannides A, Rahner N, Schanze I, Josifova D, Bocchinfuso G, Ryten M, Stella L, Tartaglia M, Zenker M.

Hum Mutat. 2020 Jun;41(6):1171-1182. doi: 10.1002/humu.24007. Epub 2020 Mar 11.

PubMed [citation]

PMID:: 32112654

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002938004.4

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

Description

This variant, c.768_770del, results in the deletion of 1 amino acid(s) of the PTPN11 protein (p.Gln257del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has been observed in individual(s) with Noonan syndrome (PMID: 32112654). ClinVar contains an entry for this variant (Variation ID: 804174). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects PTPN11 function (PMID: 32112654). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Aug 16, 2026

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