NM_000314.8(PTEN):c.1026+1G>C AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 24, 2020
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:: RCV000570522.4

Allele description [Variation Report for NM_000314.8(PTEN):c.1026+1G>C]

NM_000314.8(PTEN):c.1026+1G>C

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.1026+1G>C

HGVS:

NC_000010.11:g.87961119G>C
NG_007466.2:g.102681G>C
NM_000314.8:c.1026+1G>CMANE SELECT
NM_001304717.5:c.1546+1G>C
NM_001304718.2:c.435+1G>C
LRG_311t1:c.1026+1G>C
LRG_311:g.102681G>C
NC_000010.10:g.89720876G>C
NM_000314.4:c.1026+1G>C
NM_000314.6:c.1026+1G>C

Links:

dbSNP: rs786201041

NCBI 1000 Genomes Browser:

rs786201041

Molecular consequence:

NM_000314.8:c.1026+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001304717.5:c.1546+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001304718.2:c.435+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

Functional consequence:

sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071] - Comment(s)

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
SCV000664916	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Aug 24, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20600018, 21194675, 25669429, 28677221 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000664916

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Aug 24, 2020)

germline

clinical testing

PubMed (4)
[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

Frequent gastrointestinal polyps and colorectal adenocarcinomas in a prospective series of PTEN mutation carriers.

Heald B, Mester J, Rybicki L, Orloff MS, Burke CA, Eng C.

Gastroenterology. 2010 Dec;139(6):1927-33. doi: 10.1053/j.gastro.2010.06.061. Epub 2010 Jun 27.

PubMed [citation]

PMID:: 20600018
PMCID:: PMC3652614

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 Ambry Genetics, SCV000664916.5

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

Description

The c.1026+1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide after coding exon 8 of the PTEN gene. This variant has been detected in a cohort of patients who met clinical diagnostic criteria for Cowden syndrome (CS) or relaxed clinical diagnostic criteria for CS-like (Heald B et al. Gastroenterology. 2010 Dec;139:1927-33; Tan MH et al. Am. J. Hum. Genet. 2011 Jan;88:42-56; Nizialek EA et al. Eur. J. Hum. Genet., 2015 Nov;23:1538-43). RNA analysis showed that this variant led to abnormal splicing with retention of 190 nt from intron 8 and introduction of a stop codon at p.345 that would result in loss of amino acids encompassing exon 9 (Chen HJ et al. Hum. Mutat. 2017 10;38:1372-1377). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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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