NM_000314.8(PTEN):c.157G>A (p.Val53Ile) AND PTEN hamartoma tumor syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 1, 2022
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:: RCV003062285.3

Allele description [Variation Report for NM_000314.8(PTEN):c.157G>A (p.Val53Ile)]

NM_000314.8(PTEN):c.157G>A (p.Val53Ile)

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.157G>A (p.Val53Ile)

HGVS:

NC_000010.11:g.87894102G>A
NG_007466.2:g.35664G>A
NM_000314.8:c.157G>AMANE SELECT
NM_001304717.5:c.676G>A
NM_001304718.2:c.-549G>A
NP_000305.3:p.Val53Ile
NP_000305.3:p.Val53Ile
NP_001291646.4:p.Val226Ile
LRG_311t1:c.157G>A
LRG_311:g.35664G>A
LRG_311p1:p.Val53Ile
NC_000010.10:g.89653859G>A
NM_000314.4:c.157G>A

Protein change:

V226I

Molecular consequence:

NM_001304718.2:c.-549G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000314.8:c.157G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001304717.5:c.676G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003441578	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25669429, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003441578

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 1, 2022)

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

Citations

PubMed

KLLN epigenotype-phenotype associations in Cowden syndrome.

Nizialek EA, Mester JL, Dhiman VK, Smiraglia DJ, Eng C.

Eur J Hum Genet. 2015 Nov;23(11):1538-43. doi: 10.1038/ejhg.2015.8. Epub 2015 Feb 11.

PubMed [citation]

PMID:: 25669429
PMCID:: PMC4613489

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003441578.2

#	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PTEN protein function. This missense change has been observed in individual(s) with clinical features of PTEN-related conditions (PMID: 25669429). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 53 of the PTEN protein (p.Val53Ile).

#	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 8, 2024

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