NM_002834.5(PTPN11):c.329A>G (p.Glu110Gly) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 29, 2022
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:: RCV001825135.1

Allele description [Variation Report for NM_002834.5(PTPN11):c.329A>G (p.Glu110Gly)]

NM_002834.5(PTPN11):c.329A>G (p.Glu110Gly)

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.329A>G (p.Glu110Gly)

HGVS:

NC_000012.12:g.112450509A>G
NG_007459.1:g.36778A>G
NM_001330437.2:c.329A>G
NM_001374625.1:c.326A>G
NM_002834.5:c.329A>GMANE SELECT
NM_080601.3:c.329A>G
NP_001317366.1:p.Glu110Gly
NP_001361554.1:p.Glu109Gly
NP_002825.3:p.Glu110Gly
NP_542168.1:p.Glu110Gly
LRG_614:g.36778A>G
NC_000012.11:g.112888313A>G
NM_002834.4:c.329A>G

Protein change:

E109G

Links:

dbSNP: rs397507519

NCBI 1000 Genomes Browser:

rs397507519

Molecular consequence:

NM_001330437.2:c.329A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.326A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.329A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.329A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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CCDC7 coiled-coil domain containing 7 [Homo sapiens]
CCDC7 coiled-coil domain containing 7 [Homo sapiens]
Gene ID:79741

Gene
Gene Links for GEO Profiles (Select 108826320) (1)
Gene
25811[uid] AND (alive[prop]) (0)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002074469	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jan 29, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002074469

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jan 29, 2022)

germline

clinical testing

Citation Link

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002074469.1

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

Description

Variant summary: PTPN11 c.329A>G (p.Glu110Gly) results in a non-conservative amino acid change located in the SH2 domain (IPR000980) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251160 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.329A>G in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two different variants at the same residue, c.328G>A (p. E110K) and c.329A>C (p.E110A) have been reported in individuals affected with or referred for genetic testing for Noonan Syndrome (HGMD database and our laboratory), suggesting that this glutamate residue is clinically significant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

#	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: Nov 10, 2024

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