NM_000314.8(PTEN):c.1093G>A (p.Val365Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 20, 2023
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:: RCV000561607.9

Allele description [Variation Report for NM_000314.8(PTEN):c.1093G>A (p.Val365Ile)]

NM_000314.8(PTEN):c.1093G>A (p.Val365Ile)

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.1093G>A (p.Val365Ile)

Other names:

NM_000314.7(PTEN):c.1093G>A

HGVS:

NC_000010.11:g.87965353G>A
NG_007466.2:g.106915G>A
NM_000314.8:c.1093G>AMANE SELECT
NM_001304717.5:c.1612G>A
NM_001304718.2:c.502G>A
NP_000305.3:p.Val365Ile
NP_001291646.4:p.Val538Ile
NP_001291647.1:p.Val168Ile
LRG_311t1:c.1093G>A
LRG_311:g.106915G>A
NC_000010.10:g.89725110G>A
NM_000314.4:c.1093G>A
NM_000314.6:c.1093G>A

Protein change:

V168I

Links:

dbSNP: rs758542021

NCBI 1000 Genomes Browser:

rs758542021

Molecular consequence:

NM_000314.8:c.1093G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001304717.5:c.1612G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001304718.2:c.502G>A - missense variant - [Sequence Ontology: SO:0001583]

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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Epsilon proteobacterium LM4205 16S ribosomal RNA gene, partial sequence
Epsilon proteobacterium LM4205 16S ribosomal RNA gene, partial sequence
gi|99079502|gb|DQ517255.1|

Nucleotide
Listeria sp. LM4305 16S ribosomal RNA gene, partial sequence
Listeria sp. LM4305 16S ribosomal RNA gene, partial sequence
gi|99079503|gb|DQ517256.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000671741	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 20, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000686270	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 28, 2022)	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

SCV000671741

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 20, 2023)

germline

clinical testing

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

Citation Link,

SCV000686270

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 28, 2022)

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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Ambry Genetics, SCV000671741.6

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

Description

The p.V365I variant (also known as c.1093G>A), located in coding exon 9 of the PTEN gene, results from a G to A substitution at nucleotide position 1093. The valine at codon 365 is replaced by isoleucine, an amino acid with highly similar properties. In a massively parallel functional assay using a humanized yeast model, lipid phosphatase activity for this variant was functionally neutral (Mighell TL et al. Am J Hum Genet, 2018 05;102:943-955). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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, SCV000686270.4

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

Description

This missense variant replaces valine with isoleucine at codon 365 of the PTEN protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/239418 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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