NM_000314.8(PTEN):c.1052_1054del (p.Val351del) AND PTEN hamartoma tumor syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 23, 2020
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000710313.8

Allele description [Variation Report for NM_000314.8(PTEN):c.1052_1054del (p.Val351del)]

NM_000314.8(PTEN):c.1052_1054del (p.Val351del)

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.1052_1054del (p.Val351del)

Other names:

NM_000314.6(PTEN):c.1052_1054delTAG(p.Val351del)

HGVS:

NC_000010.11:g.87965312_87965314del
NG_007466.2:g.106874_106876del
NM_000314.8:c.1052_1054delMANE SELECT
NM_001304717.5:c.1571_1573del
NM_001304718.2:c.461_463del
NP_000305.3:p.Val351del
NP_001291646.4:p.Val524del
NP_001291647.1:p.Val154del
LRG_311t1:c.1052_1054del
LRG_311:g.106874_106876del
NC_000010.10:g.89725067_89725069del
NC_000010.10:g.89725069_89725071del
NC_000010.11:g.87965312_87965314delTAG
NM_000314.4:c.1052_1054delTAG
NM_000314.6(PTEN):c.1052_1054delTAG
NM_000314.6:c.1052_1054del
NM_000314.6:c.1052_1054delTAG
p.V351del

Protein change:

V154del

Links:

dbSNP: rs587780003

NCBI 1000 Genomes Browser:

rs587780003

Molecular consequence:

NM_000314.8:c.1052_1054del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001304717.5:c.1571_1573del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001304718.2:c.461_463del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: PTEN hamartoma tumor syndrome (PHTS)
Synonyms:: PTEN Hamartomatous Tumour Syndrome
Identifiers:: MONDO: MONDO:0017623; MeSH: D006223; MedGen: C1959582

Recent activity

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gi|1889731428|ref|NM_138385.4|

Nucleotide
Vibrio anguillarum strain PF4-E1-2 chromosome 1
Vibrio anguillarum strain PF4-E1-2 chromosome 1
gi|1447619076|gb|CP031481.1|

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Homo sapiens myosin, heavy chain 7, cardiac muscle, beta, mRNA (cDNA clone MGC:1...
Homo sapiens myosin, heavy chain 7, cardiac muscle, beta, mRNA (cDNA clone MGC:138378 IMAGE:8327641), complete cds
gi|85567023|gb|BC112173.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000840493	Clingen PTEN Variant Curation Expert Panel, Clingen	reviewed by expert panel (ClinGen PTEN ACMG Specifications v2)	Uncertain significance (Mar 23, 2020)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002134502	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 5, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29706350, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000840493

Clingen PTEN Variant Curation Expert Panel, Clingen

reviewed by expert panel

(ClinGen PTEN ACMG Specifications v2)

Uncertain significance
(Mar 23, 2020)

germline

curation

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

Citation Link,

SCV002134502

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 5, 2021)

germline

clinical testing

PubMed (2)
[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, curation

Citations

PubMed

A Saturation Mutagenesis Approach to Understanding PTEN Lipid Phosphatase Activity and Genotype-Phenotype Relationships.

Mighell TL, Evans-Dutson S, O'Roak BJ.

Am J Hum Genet. 2018 May 3;102(5):943-955. doi: 10.1016/j.ajhg.2018.03.018. Epub 2018 Apr 26.

PubMed [citation]

PMID:: 29706350
PMCID:: PMC5986715

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Clingen PTEN Variant Curation Expert Panel, Clingen, SCV000840493.2

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

Description

PTEN c.1052_1054delTAG (p.Val351del) is currently classified as a variant of uncertain significance for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). PM2: Absent in large sequenced populations (PMID 27535533). BS3_P: In vitro or in vivo functional study or studies showing no damaging effect on protein function but BS3 not met. (PMID 29706350)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002134502.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this variant does not substantially affect PTEN protein function (PMID: 29706350). This variant has not been reported in the literature in individuals with PTEN-related conditions. ClinVar contains an entry for this variant (Variation ID: 127687). This variant is not present in population databases (ExAC no frequency). This variant, c.1052_1054del, results in the deletion of 1 amino acid(s) of the PTEN protein (p.Val351del), but otherwise preserves the integrity of the reading frame.

#	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 20, 2024

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