NM_000314.8(PTEN):c.1105G>A (p.Val369Ile) AND PTEN hamartoma tumor syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 23, 2020
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000556721.9

Allele description [Variation Report for NM_000314.8(PTEN):c.1105G>A (p.Val369Ile)]

NM_000314.8(PTEN):c.1105G>A (p.Val369Ile)

Gene:

PTEN:phosphatase and tensin homolog [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q23.31

Genomic location:

Preferred name:

NM_000314.8(PTEN):c.1105G>A (p.Val369Ile)

HGVS:

NC_000010.11:g.87965365G>A
NG_007466.2:g.106927G>A
NM_000314.8:c.1105G>AMANE SELECT
NM_001304717.5:c.1624G>A
NM_001304718.2:c.514G>A
NP_000305.3:p.Val369Ile
NP_001291646.4:p.Val542Ile
NP_001291647.1:p.Val172Ile
LRG_311t1:c.1105G>A
LRG_311:g.106927G>A
NC_000010.10:g.89725122G>A
NC_000010.10:g.89725122G>A
NM_000314.4:c.1105G>A
NM_000314.7(PTEN):c.1105G>A
p.V369I
p.Val369Ile

Protein change:

V172I

Links:

dbSNP: rs587782224

NCBI 1000 Genomes Browser:

rs587782224

Molecular consequence:

NM_000314.8:c.1105G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001304717.5:c.1624G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001304718.2:c.514G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: PTEN hamartoma tumor syndrome (PHTS)
Synonyms:: PTEN Hamartomatous Tumour Syndrome
Identifiers:: MONDO: MONDO:0017623; MeSH: D006223; MedGen: C1959582

Recent activity

Clear Turn Off Turn On

TSA: Hypotaenidia okinawae RNA, GAOK03217, transcribed RNA sequence
TSA: Hypotaenidia okinawae RNA, GAOK03217, transcribed RNA sequence
gi|1820499569|dbj|ICPP01003212.1||g A:ICPP01|GAOK03217

Nucleotide
TSA: Hypotaenidia okinawae RNA, GAOK03188, transcribed RNA sequence
TSA: Hypotaenidia okinawae RNA, GAOK03188, transcribed RNA sequence
gi|1820499627|dbj|ICPP01003183.1||g A:ICPP01|GAOK03188

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000645546	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 4, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29706350, 28492532
SCV001335272	Clingen PTEN Variant Curation Expert Panel, Clingen	reviewed by expert panel (ClinGen PTEN ACMG Specifications v2)	Uncertain significance (Mar 23, 2020)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000645546

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 4, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001335272

Clingen PTEN Variant Curation Expert Panel, Clingen

reviewed by expert panel

(ClinGen PTEN ACMG Specifications v2)

Uncertain significance
(Mar 23, 2020)

germline

curation

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

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, curation

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

A Saturation Mutagenesis Approach to Understanding PTEN Lipid Phosphatase Activity and Genotype-Phenotype Relationships.

Mighell TL, Evans-Dutson S, O'Roak BJ.

Am J Hum Genet. 2018 May 3;102(5):943-955. doi: 10.1016/j.ajhg.2018.03.018. Epub 2018 Apr 26.

PubMed [citation]

PMID:: 29706350
PMCID:: PMC5986715

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000645546.4

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

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. ClinVar contains an entry for this variant (Variation ID: 142088). Experimental studies have shown that this missense change does not substantially affect PTEN function (PMID: 29706350). 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 not expected to disrupt PTEN protein function. This variant has not been reported in the literature in individuals affected with PTEN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 369 of the PTEN protein (p.Val369Ile).

#	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

From Clingen PTEN Variant Curation Expert Panel, Clingen, SCV001335272.1

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

Description

PTEN c.1105G>A (p.Val369Ile) is currently classified as a variant of uncertain significance for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). PM2: Absent in large sequenced populations PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease BS3_P: In vitro or in vivo functional study or studies showing no damaging effect on protein function but BS3 not met. (PMID 29706350)

#	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

ClinVar

Relating variation to medicine