NM_000314.8(PTEN):c.1137T>G (p.Tyr379Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 18, 2019
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:: RCV001009950.3

Allele description [Variation Report for NM_000314.8(PTEN):c.1137T>G (p.Tyr379Ter)]

NM_000314.8(PTEN):c.1137T>G (p.Tyr379Ter)

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.1137T>G (p.Tyr379Ter)

HGVS:

NC_000010.11:g.87965397T>G
NG_007466.2:g.106959T>G
NM_000314.8:c.1137T>GMANE SELECT
NM_001304717.5:c.1656T>G
NM_001304718.2:c.546T>G
NP_000305.3:p.Tyr379Ter
NP_001291646.4:p.Tyr552Ter
NP_001291647.1:p.Tyr182Ter
LRG_311t1:c.1137T>G
LRG_311:g.106959T>G
NC_000010.10:g.89725154T>G
NM_000314.4:c.1137T>G

Protein change:

Y182*

Links:

dbSNP: rs1295420243

NCBI 1000 Genomes Browser:

rs1295420243

Molecular consequence:

NM_000314.8:c.1137T>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001304717.5:c.1656T>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001304718.2:c.546T>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001170083	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Sep 18, 2019)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10468583, 10866658, 19114656, 20940307, 24561254 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001170083

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Sep 18, 2019)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Citations

PubMed

The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region.

Georgescu MM, Kirsch KH, Akagi T, Shishido T, Hanafusa H.

Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10182-7.

PubMed [citation]

PMID:: 10468583
PMCID:: PMC17863

Phosphorylation of the PTEN tail regulates protein stability and function.

Vazquez F, Ramaswamy S, Nakamura N, Sellers WR.

Mol Cell Biol. 2000 Jul;20(14):5010-8.

PubMed [citation]

PMID:: 10866658
PMCID:: PMC85951

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV001170083.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The p.Y379* variant (also known as c.1137T>G), located in coding exon 9 of the PTEN gene, results from a T to G substitution at nucleotide position 1137. This changes the amino acid from a tyrosine to a stop codon within coding exon 9. This stop codon occurs at the 3' terminus of PTEN, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 25 amino acids of the protein. Experimental literature points to this region being crucial for regulation of PTEN activity (Georgescu MM et al. Proc. Natl. Acad. Sci. U.S.A., 1999 Aug;96:10182-7; Hopkins BD et al. Trends Biochem. Sci., 2014 Apr;39:183-90; Sun Z et al. Cell Rep, 2014 Mar;6:844-54; Vazquez F et al. Mol. Cell. Biol., 2000 Jul;20:5010-8). Based on the majority of available evidence to date, this variant is likely to be 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: May 1, 2024

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