NM_000314.8(PTEN):c.314G>A (p.Cys105Tyr) AND PTEN hamartoma tumor syndrome

Clinical significance:Likely pathogenic (Last evaluated: Nov 28, 2018)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000549505.2

Allele description [Variation Report for NM_000314.8(PTEN):c.314G>A (p.Cys105Tyr)]

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

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.314G>A (p.Cys105Tyr)
Other names:
NM_000314.6(PTEN):c.314G>A
HGVS:
  • 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:
C105Y
Links:
UniProtKB: P60484#VAR_008735; dbSNP: rs587782343
NCBI 1000 Genomes Browser:
rs587782343
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]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000645568Invitaecriteria provided, single submitter
Uncertain significance
(Jul 26, 2017)
germlineclinical testing

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

SCV000930141ClinGen PTEN Variant Curation Expert Panelreviewed by expert panel
Likely pathogenic
(Nov 28, 2018)
germlinecuration

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation

Citations

PubMed

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Analysis of protein-coding genetic variation in 60,706 humans.

Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, et al.

Nature. 2016 Aug 18;536(7616):285-91. doi: 10.1038/nature19057.

PubMed [citation]
PMID:
27535533
PMCID:
PMC5018207

Details of each submission

From Invitae, SCV000645568.1

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

Description

This sequence change replaces cysteine with tyrosine at codon 105 of the PTEN protein (p.Cys105Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Bannayan-Riley-Ruvalcaba syndrome (PMID: 10400993). ClinVar contains an entry for this variant (Variation ID: 142261). An experimental study has reported that this missense change impairs the interaction of PTEN and LKB1 protein in a yeast two-hybrid assay, however the clinical significance of this result is uncertain (PMID: 15987703). 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 ClinGen PTEN Variant Curation Expert Panel, SCV000930141.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

PTEN c.314G>A (p.Cys105Tyr) meets criteria to be classified as likely pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). PM2: Absent in large sequenced populations (PMID 27535533). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (internal laboratory contributor ClinVar Organization ID 26957) PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (internal laboratory contributor ClinVar Organization ID 26957)

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

Last Updated: Oct 30, 2021

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