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NM_000314.8(PTEN):c.1066A>G (p.Asn356Asp) AND PTEN hamartoma tumor syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Dec 27, 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:
RCV000463640.11

Allele description [Variation Report for NM_000314.8(PTEN):c.1066A>G (p.Asn356Asp)]

NM_000314.8(PTEN):c.1066A>G (p.Asn356Asp)

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.1066A>G (p.Asn356Asp)
HGVS:
  • NC_000010.11:g.87965326A>G
  • NG_007466.2:g.106888A>G
  • NM_000314.8:c.1066A>GMANE SELECT
  • NM_001304717.5:c.1585A>G
  • NM_001304718.2:c.475A>G
  • NP_000305.3:p.Asn356Asp
  • NP_001291646.4:p.Asn529Asp
  • NP_001291647.1:p.Asn159Asp
  • LRG_311t1:c.1066A>G
  • LRG_311:g.106888A>G
  • NC_000010.10:g.89725083A>G
  • NM_000314.4:c.1066A>G
  • NM_000314.6:c.1066A>G
  • p.N356D
Protein change:
N159D
Links:
dbSNP: rs587782345
NCBI 1000 Genomes Browser:
rs587782345
Molecular consequence:
  • NM_000314.8:c.1066A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001304717.5:c.1585A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001304718.2:c.475A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000541613Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 27, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004838602All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(May 23, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical testing

Citations

PubMed

A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands.

Tan MH, Mester J, Peterson C, Yang Y, Chen JL, Rybicki LA, Milas K, Pederson H, Remzi B, Orloff MS, Eng C.

Am J Hum Genet. 2011 Jan 7;88(1):42-56. doi: 10.1016/j.ajhg.2010.11.013. Epub 2010 Dec 30.

PubMed [citation]
PMID:
21194675
PMCID:
PMC3014373

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
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000541613.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 356 of the PTEN protein (p.Asn356Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with PTEN hamartoma tumor syndrome (PHTS) (PMID: 21194675). ClinVar contains an entry for this variant (Variation ID: 142263). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt PTEN function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect PTEN function (PMID: 29706350, 32350270). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004838602.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024