NM_000314.8(PTEN):c.654C>A (p.Cys218Ter) AND PTEN hamartoma tumor syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 14, 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:: RCV003509605.1

Allele description

NM_000314.8(PTEN):c.654C>A (p.Cys218Ter)

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.654C>A (p.Cys218Ter)

HGVS:

NC_000010.11:g.87957872C>A
NG_007466.2:g.99434C>A
NM_000314.4:c.654C>A
NM_000314.8:c.654C>AMANE SELECT
NM_001304717.5:c.1173C>A
NM_001304718.2:c.63C>A
NP_000305.3:p.Cys218Ter
NP_001291646.4:p.Cys391Ter
NP_001291647.1:p.Cys21Ter
LRG_311t1:c.654C>A
LRG_311:g.99434C>A
NC_000010.10:g.89717629C>A
NM_000314.6:c.654C>A

Protein change:

C21*

Links:

dbSNP: rs1554825165

NCBI 1000 Genomes Browser:

rs1554825165

Molecular consequence:

NM_000314.8:c.654C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001304717.5:c.1173C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001304718.2:c.63C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: PTEN hamartoma tumor syndrome (PHTS)
Synonyms:: PTEN Hamartomatous Tumour Syndrome; PTEN-related disorders
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
SCV004295314	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 14, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9467011, 21194675, 22970944, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004295314

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 14, 2023)

germline

clinical testing

PubMed (4)
[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

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.

Marsh DJ, Coulon V, Lunetta KL, Rocca-Serra P, Dahia PL, Zheng Z, Liaw D, Caron S, Duboué B, Lin AY, Richardson AL, Bonnetblanc JM, Bressieux JM, Cabarrot-Moreau A, Chompret A, Demange L, Eeles RA, Yahanda AM, Fearon ER, Fricker JP, Gorlin RJ, Hodgson SV, et al.

Hum Mol Genet. 1998 Mar;7(3):507-15.

PubMed [citation]

PMID:: 9467011

A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands.

Tan MH, Mester J, Peterson C, Yang Y, Chen JL, Rybicki LA, Milas K, Pederson H, Remzi B, Orloff MS, Eng C.

Am J Hum Genet. 2011 Jan 7;88(1):42-56. doi: 10.1016/j.ajhg.2010.11.013. Epub 2010 Dec 30.

PubMed [citation]

PMID:: 21194675
PMCID:: PMC3014373

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004295314.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Cys218*) in the PTEN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Cowden syndrome (PMID: 22970944). ClinVar contains an entry for this variant (Variation ID: 631516). For these reasons, this variant has been classified as 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: Feb 20, 2024

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