NM_000314.7(PTEN):c.830C>G (p.Thr277Arg) AND Hereditary cancer-predisposing syndrome

Clinical significance:Likely pathogenic (Last evaluated: Apr 15, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000314.7(PTEN):c.830C>G (p.Thr277Arg)]

NM_000314.7(PTEN):c.830C>G (p.Thr277Arg)

PTEN:phosphatase and tensin homolog [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000314.7(PTEN):c.830C>G (p.Thr277Arg)
  • NC_000010.11:g.87960922C>G
  • NG_007466.2:g.102484C>G
  • NM_000314.7:c.830C>G
  • NM_001304717.5:c.1349C>G
  • NM_001304718.2:c.239C>G
  • NP_000305.3:p.Thr277Arg
  • NP_001291646.4:p.Thr450Arg
  • NP_001291647.1:p.Thr80Arg
  • LRG_311t1:c.830C>G
  • LRG_311:g.102484C>G
  • NC_000010.10:g.89720679C>G
  • NM_000314.4:c.830C>G
  • NM_000314.7(PTEN):c.830C>G
  • p.Thr277Arg
Protein change:
dbSNP: rs398123329
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000314.7:c.830C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001304717.5:c.1349C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001304718.2:c.239C>G - missense variant - [Sequence Ontology: SO:0001583]


Hereditary cancer-predisposing syndrome
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000580063Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Apr 15, 2016)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing



Cellular transformation by the MSP58 oncogene is inhibited by its physical interaction with the PTEN tumor suppressor.

Okumura K, Zhao M, Depinho RA, Furnari FB, Cavenee WK.

Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2703-6. Epub 2005 Jan 19.

PubMed [citation]

Molecular apocrine differentiation is a common feature of breast cancer in patients with germline PTEN mutations.

Banneau G, Guedj M, MacGrogan G, de Mascarel I, Velasco V, Schiappa R, Bonadona V, David A, Dugast C, Gilbert-Dussardier B, Ingster O, Vabres P, Caux F, de Reynies A, Iggo R, Sevenet N, Bonnet F, Longy M.

Breast Cancer Res. 2010;12(4):R63. doi: 10.1186/bcr2626. Epub 2010 Aug 16.

PubMed [citation]
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000580063.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (4)


<span style="font-size:12px"><span style="font-family:arial,helvetica,sans-serif">The p.T277R variant (also known as c.830C>G), located in coding exon 8 of the PTEN gene, results from a C to G substitution at nucleotide position 830. The threonine at codon 277 is replaced by arginine, an amino acid with similar properties. This alteration was detected in the germline of an individual diagnosed withCowden syndrome (CS) and breast cancer. This individual's tumor was noted to have an expression profile similar to that of other CS breast tumors, and absent PTENIHC expression (BanneauG, Breast Cancer Res. 2010;12(4):R63). This residue occurs in a match for a FHA domain consensus recognition sequence, suggesting that it is a potential binding site(Okumura K et al.Proc. Natl. Acad. Sci. U.S.A. 2005 Feb;102(8):2703-6). In addition, the destabilizing energy of thisvariant is significantly greaterthan a known pathogenic variant in the same amino acidposition(Ambry internal data).This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6480 samples (12960 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 200000 alleles tested) in our clinical cohort.This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis.Based on the majority of available evidence to date, this variant is likely to be pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Jul 24, 2021

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