NM_002834.5(PTPN11):c.983T>C (p.Ile328Thr) AND RASopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 11, 2020
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:: RCV001992792.6

Allele description [Variation Report for NM_002834.5(PTPN11):c.983T>C (p.Ile328Thr)]

NM_002834.5(PTPN11):c.983T>C (p.Ile328Thr)

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.983T>C (p.Ile328Thr)

HGVS:

NC_000012.12:g.112477906T>C
NG_007459.1:g.64175T>C
NM_001330437.2:c.983T>C
NM_001374625.1:c.980T>C
NM_002834.3:c.983T>C
NM_002834.5:c.983T>CMANE SELECT
NM_080601.3:c.983T>C
NP_001317366.1:p.Ile328Thr
NP_001361554.1:p.Ile327Thr
NP_002825.3:p.Ile328Thr
NP_542168.1:p.Ile328Thr
LRG_614t1:c.983T>C
LRG_614:g.64175T>C
NC_000012.11:g.112915710T>C

Protein change:

I327T

Links:

dbSNP: rs369430257

NCBI 1000 Genomes Browser:

rs369430257

Molecular consequence:

NM_001330437.2:c.983T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.980T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.983T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.983T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002226825	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 11, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002226825

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 11, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV002226825.3

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

Description

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. 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. This variant has not been reported in the literature in individuals with PTPN11-related conditions. This variant is present in population databases (rs369430257, ExAC 0.01%). This sequence change replaces isoleucine with threonine at codon 328 of the PTPN11 protein (p.Ile328Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine.

#	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: Sep 29, 2024

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