NM_000314.8(PTEN):c.738_743del (p.Leu247_Pro248del) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 22, 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:: RCV000490881.3

Allele description [Variation Report for NM_000314.8(PTEN):c.738_743del (p.Leu247_Pro248del)]

NM_000314.8(PTEN):c.738_743del (p.Leu247_Pro248del)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

10q23.31

Genomic location:

Preferred name:

NM_000314.8(PTEN):c.738_743del (p.Leu247_Pro248del)

HGVS:

NC_000010.11:g.87957956_87957961del
NG_007466.2:g.99518_99523del
NM_000314.8:c.738_743delMANE SELECT
NM_001304717.5:c.1257_1262del
NM_001304718.2:c.147_152del
NP_000305.3:p.Leu247_Pro248del
NP_001291646.4:p.Leu420_Pro421del
NP_001291647.1:p.Leu50_Pro51del
LRG_311t1:c.738_743del
LRG_311:g.99518_99523del
NC_000010.10:g.89717713_89717718del
NM_000314.4:c.738_743delGTTACC

Links:

dbSNP: rs1114167666

NCBI 1000 Genomes Browser:

rs1114167666

Molecular consequence:

NM_000314.8:c.738_743del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001304717.5:c.1257_1262del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001304718.2:c.147_152del - inframe_deletion - [Sequence Ontology: SO:0001822]

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

Recent activity

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Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/human/AUS/VIC...
Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/human/AUS/VIC-CBA6/2020 ORF1ab polyprotein (ORF1ab) gene, partial cds; ORF1a polyprotein (ORF1ab) gene, complete cds; surface glycoprotein (S) gene, partial cds; and ORF3a protein (ORF3a), envelope protein (E), membrane glycoprotein (M), ORF6 protein (ORF6), ORF7a protein (ORF7a), ORF7b (ORF7b), ORF8 protein (ORF8), nucleocapsid phosphoprotein (N), and ORF10 protein (ORF10) genes, complete cds
gi|1927695169|gb|MW193406.1|

Nucleotide
12610527 AND 1[s_discriminator] (0)
dbGaP
YJL062W (0)
GEO DataSets

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000580047	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Oct 22, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10555148, 25851949, 29533785 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000580047

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Oct 22, 2019)

germline

clinical testing

PubMed (3)
[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

Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.

Lee JO, Yang H, Georgescu MM, Di Cristofano A, Maehama T, Shi Y, Dixon JE, Pandolfi P, Pavletich NP.

Cell. 1999 Oct 29;99(3):323-34.

PubMed [citation]

PMID:: 10555148

PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels.

Choi Y, Chan AP.

Bioinformatics. 2015 Aug 15;31(16):2745-7. doi: 10.1093/bioinformatics/btv195. Epub 2015 Apr 6.

PubMed [citation]

PMID:: 25851949
PMCID:: PMC4528627

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000580047.6

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

Description

The c.738_743delGTTACC variant (also known as p.L247_P248del) is located in coding exon 7 of the PTEN gene. This variant results from an in-frame deletion of GTTACC between nucleotide positions 738 and 743. This results in the deletion of a highly conserved leucine residue at codon 247 and a highly conserved proline residue at codon 248. This variant was identified in an individual meeting clinical diagnostic criteria for PTEN hamartoma tumor syndrome (Ambry internal data). This variant also demonstrated aberrant activity in cell viability assays (Ng PK et al. Cancer Cell, 2018 03;33:450-462.e10). Based on internal structural analysis, p.L247 and p.P248 reside within a β-sandwich on the C2 domain directed towards the phosphatase domain and the p.L247_P248del alteration results in a distortion of this β-sandwich significantly altering the surrounding residues (Lee JO et al. Cell, 1999 Oct;99:323-34). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD) (Lek M et al. Nature, 2016 08;536:285-91). In addition, this alteration is predicted to be deleterious by PROVEAN in silico analysis (Choi Y et al., Bioinformatics 2015 Aug; 31(16):2745-7). 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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