NM_000314.8(PTEN):c.314G>A (p.Cys105Tyr) AND Hereditary cancer-predisposing syndrome

Clinical significance:Uncertain significance (Last evaluated: May 24, 2018)

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_000314.8(PTEN):c.314G>A (p.Cys105Tyr)]

NM_000314.8(PTEN):c.314G>A (p.Cys105Tyr)

PTEN:phosphatase and tensin homolog [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000314.8(PTEN):c.314G>A (p.Cys105Tyr)
Other names:
  • NC_000010.11:g.87933073G>A
  • NG_007466.2:g.74635G>A
  • NM_000314.8:c.314G>AMANE SELECT
  • NM_001304717.5:c.833G>A
  • NM_001304718.2:c.-437G>A
  • NP_000305.3:p.Cys105Tyr
  • NP_001291646.4:p.Cys278Tyr
  • LRG_311t1:c.314G>A
  • LRG_311:g.74635G>A
  • NC_000010.10:g.89692830G>A
  • NM_000314.4:c.314G>A
  • P60484:p.Cys105Tyr
  • p.C105Y
Protein change:
UniProtKB: P60484#VAR_008735; dbSNP: rs587782343
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001304718.2:c.-437G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000314.8:c.314G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001304717.5:c.833G>A - 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)
SCV000186248Ambry Geneticscriteria provided, single submitter
Uncertain significance
(May 24, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing



PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome.

Marsh DJ, Kum JB, Lunetta KL, Bennett MJ, Gorlin RJ, Ahmed SF, Bodurtha J, Crowe C, Curtis MA, Dasouki M, Dunn T, Feit H, Geraghty MT, Graham JM Jr, Hodgson SV, Hunter A, Korf BR, Manchester D, Miesfeldt S, Murday VA, Nathanson KL, Parisi M, et al.

Hum Mol Genet. 1999 Aug;8(8):1461-72.

PubMed [citation]

LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes.

Mehenni H, Lin-Marq N, Buchet-Poyau K, Reymond A, Collart MA, Picard D, Antonarakis SE.

Hum Mol Genet. 2005 Aug 1;14(15):2209-19. Epub 2005 Jun 29.

PubMed [citation]

Details of each submission

From Ambry Genetics, SCV000186248.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)


​The p.C105Y variant (also known as c.314G>A) is located in coding exon 5 of the PTEN gene. This alteration results from a G to A substitution at nucleotide position 314. The cysteine at codon 105 is replaced by tyrosine, an amino acid with highly dissimilar properties. This variant was observed in 1 of 43 individuals who were clinically diagnosed with Bannayan-Riley-Ruvalcaba (BRR) syndrome (Marsh, DJ. Hum Mol Genet. 1999 Aug;8(8):1461-72). In one functional study, the PTEN p.C105Y variant showed no interaction with the LKB1 (STK11) protein in a yeast two-hybrid assay (Mehenni H et al. Hum. Mol. Genet., 2005 Aug;14:2209-19). Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Oct 30, 2021

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