NM_000314.8(PTEN):c.1204A>G (p.Lys402Glu) AND PTEN hamartoma tumor syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 22, 2023
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:: RCV000645067.8

Allele description [Variation Report for NM_000314.8(PTEN):c.1204A>G (p.Lys402Glu)]

NM_000314.8(PTEN):c.1204A>G (p.Lys402Glu)

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.1204A>G (p.Lys402Glu)

HGVS:

NC_000010.11:g.87965464A>G
NG_007466.2:g.107026A>G
NM_000314.8:c.1204A>GMANE SELECT
NM_001304717.5:c.1723A>G
NM_001304718.2:c.613A>G
NP_000305.3:p.Lys402Glu
NP_001291646.4:p.Lys575Glu
NP_001291647.1:p.Lys205Glu
LRG_311t1:c.1204A>G
LRG_311:g.107026A>G
NC_000010.10:g.89725221A>G
NM_000314.4:c.1204A>G

Protein change:

K205E

Links:

dbSNP: rs1554826064

NCBI 1000 Genomes Browser:

rs1554826064

Molecular consequence:

NM_000314.8:c.1204A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001304717.5:c.1723A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001304718.2:c.613A>G - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000766808	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 22, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25448478, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000766808

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 22, 2023)

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

PTEN-PDZ domain interactions: binding of PTEN to PDZ domains of PTPN13.

Sotelo NS, Schepens JT, Valiente M, Hendriks WJ, Pulido R.

Methods. 2015 May;77-78:147-56. doi: 10.1016/j.ymeth.2014.10.017. Epub 2014 Oct 22.

PubMed [citation]

PMID:: 25448478

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, SCV000766808.4

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

Description

Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on PTEN function (PMID: 25448478). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 402 of the PTEN protein (p.Lys402Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PTEN-related conditions. ClinVar contains an entry for this variant (Variation ID: 536557).

#	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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