NM_000314.8(PTEN):c.464A>G (p.Tyr155Cys) AND Hereditary cancer-predisposing syndrome

Clinical significance:Likely pathogenic (Last evaluated: Aug 19, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001022838.1

Allele description [Variation Report for NM_000314.8(PTEN):c.464A>G (p.Tyr155Cys)]

NM_000314.8(PTEN):c.464A>G (p.Tyr155Cys)

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.464A>G (p.Tyr155Cys)
HGVS:
  • NC_000010.11:g.87933223A>G
  • NG_007466.2:g.74785A>G
  • NM_000314.8:c.464A>GMANE SELECT
  • NM_001304717.5:c.983A>G
  • NM_001304718.2:c.-287A>G
  • NP_000305.3:p.Tyr155Cys
  • NP_001291646.4:p.Tyr328Cys
  • LRG_311t1:c.464A>G
  • LRG_311:g.74785A>G
  • NC_000010.10:g.89692980A>G
  • NM_000314.4:c.464A>G
  • NM_000314.6:c.464A>G
  • NM_000314.7(PTEN):c.464A>G
  • p.Tyr155Cys
Protein change:
Y155C
Links:
dbSNP: rs1060500126
NCBI 1000 Genomes Browser:
rs1060500126
Molecular consequence:
  • NM_001304718.2:c.-287A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000314.8:c.464A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001304717.5:c.983A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001184619Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Aug 19, 2019)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Retinal angioma in a patient with Cowden disease.

Gicquel JJ, Vabres P, Bonneau D, MerciƩ M, Handiri L, Dighiero P.

Am J Ophthalmol. 2003 Mar;135(3):400-2.

PubMed [citation]
PMID:
12614768

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
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV001184619.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (6)

Description

The p.Y155C variant (also known as c.464A>G), located in coding exon 5 of the PTEN gene, results from an A to G substitution at nucleotide position 464. The tyrosine at codon 155 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant has been reported in individuals meeting at least relaxed Cowden syndrome criteria as well as classic Cowden syndrome criteria (Tan MH et al. Am. J. Hum. Genet. 2011 Jan; 88(1):42-56; Gicquel JJ et al. Am. J. Ophthalmol. 2003 Mar; 135(3):400-2; Bubien V et al. J. Med. Genet., 2013 Apr;50:255-63; Ngeow J et al. Gastroenterology, 2013 Jun;144:1402-9, 1409.e1-5; Nizialek E et al. Eur. J. Hum. Genet. 2015 Nov;23(11):1538-43; Driessen GJ et al. J. Allergy Clin. Immunol., 2016 12;138:1744-1747.e5; Ambry internal data). In a yeast functional assay, this variant demonstrated loss of in vivo phosphatase activity (Rodríguez-Escudero I et al. Hum. Mol. Genet. 2011 Nov; 20(21):4132-42). 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.

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

Last Updated: Aug 27, 2021

Support Center