NM_000314.8(PTEN):c.741dup (p.Pro248fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 5, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000131274.9

Allele description [Variation Report for NM_000314.8(PTEN):c.741dup (p.Pro248fs)]

NM_000314.8(PTEN):c.741dup (p.Pro248fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

10q23.31

Genomic location:

Preferred name:

NM_000314.8(PTEN):c.741dup (p.Pro248fs)

HGVS:

NC_000010.11:g.87957959dup
NG_007466.2:g.99521dup
NM_000314.8:c.741dupMANE SELECT
NM_001304717.5:c.1260dup
NM_001304718.2:c.150dup
NP_000305.3:p.Pro248fs
NP_001291646.4:p.Pro421fs
NP_001291647.1:p.Pro51fs
LRG_311t1:c.741dup
LRG_311:g.99521dup
NC_000010.10:g.89717715_89717716insA
NC_000010.10:g.89717716dup
NM_000314.4:c.741dup
NM_000314.4:c.741dupA
NM_000314.6:c.741dup
p.P248Tfs*5

Protein change:

P248fs

Links:

dbSNP: rs587782341

NCBI 1000 Genomes Browser:

rs587782341

Molecular consequence:

NM_000314.8:c.741dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001304717.5:c.1260dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001304718.2:c.150dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000186242	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Nov 5, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23423780, 29927861, 31336731 Citation Link,
SCV001339382	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 15, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000186242

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Nov 5, 2020)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV001339382

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 15, 2020)

germline

clinical testing

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

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

Autosomal Dominant Inherited Cowden's Disease in a Family.

Ha JW.

Clin Endosc. 2013 Jan;46(1):85-90. doi: 10.5946/ce.2013.46.1.85. Epub 2013 Jan 31.

PubMed [citation]

PMID:: 23423780
PMCID:: PMC3572359

Diffuse Intestinal Ganglioneuromatosis Causing Severe Intestinal Dysmotility in a Child With a PTEN Mutation.

Rosenfeld EH, Chumpitazi BP, Castro E, Naik-Mathuria B.

J Pediatr Gastroenterol Nutr. 2019 Feb;68(2):e35-e37. doi: 10.1097/MPG.0000000000002072. No abstract available.

PubMed [citation]

PMID:: 29927861

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000186242.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.741dupA pathogenic mutation, located in coding exon 7 of the PTEN gene, results from a duplication of A at nucleotide position 741, causing a translational frameshift with a predicted alternate stop codon (p.P248Tfs*5). This alteration has been reported in multiple individuals with personal history consistent with PTEN Hamartoma Tumor Syndrome (Ha JW. Clin Endosc, 2013 Jan;46:85-90; Plamper M et al. Cancers (Basel), 2019 Jul;11; Rosenfeld EH et al. J Pediatr Gastroenterol Nutr, 2019 Feb;68:e35-e37). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, 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

From Color Diagnostics, LLC DBA Color Health, SCV001339382.2

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

Description

This variant inserts 1 nucleotide in exon 7 of the PTEN gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 1/251432 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of PTEN function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is 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: Oct 26, 2024

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