NM_000314.8(PTEN):c.182A>G (p.His61Arg) AND Hereditary cancer-predisposing syndrome

Clinical significance:Likely pathogenic (Last evaluated: Oct 10, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000491953.1

Allele description [Variation Report for NM_000314.8(PTEN):c.182A>G (p.His61Arg)]

NM_000314.8(PTEN):c.182A>G (p.His61Arg)

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.182A>G (p.His61Arg)
HGVS:
  • NC_000010.11:g.87925530A>G
  • NG_007466.2:g.67092A>G
  • NM_000314.8:c.182A>GMANE SELECT
  • NM_001304717.5:c.701A>G
  • NM_001304718.2:c.-541-5516A>G
  • NP_000305.3:p.His61Arg
  • NP_001291646.4:p.His234Arg
  • LRG_311t1:c.182A>G
  • LRG_311:g.67092A>G
  • NC_000010.10:g.89685287A>G
  • NM_000314.4:c.182A>G
  • NM_000314.6:c.182A>G
  • P60484:p.His61Arg
Protein change:
H234R
Links:
UniProtKB: P60484#VAR_026253; dbSNP: rs398123316
NCBI 1000 Genomes Browser:
rs398123316
Molecular consequence:
  • NM_001304718.2:c.-541-5516A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000314.8:c.182A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001304717.5:c.701A>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
SCV000579972Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Oct 10, 2019)
germlineclinical testing

PubMed (3)
[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

A novel germline mutation of the PTEN gene in a patient with macrocephaly, ventricular dilatation, and features of VATER association.

Reardon W, Zhou XP, Eng C.

J Med Genet. 2001 Dec;38(12):820-3.

PubMed [citation]
PMID:
11748304
PMCID:
PMC1734782

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 (3)

Details of each submission

From Ambry Genetics, SCV000579972.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

​The p.H61R variant (also known as c.182A>G) is located in coding exon 3 of the PTEN gene. This alteration results from an A to G substitution at nucleotide position 182. The histidine at codon 61 is replaced by arginine, an amino acid with similar properties. This alteration has been reported in individuals meeting relaxed International Cowden Consortium operational criteria for Cowden syndrome (Tan MH et al. Am J Hum Genet. 2011 Jan 7;88(1):42-56), as well as an individual with Bannayan-Riley-Ruvalcaba syndrome (Hansen-Kiss E et al. J. Med. Genet. 2017 07;54:471-478). Another mutation has also been reported at the same codon (p.H61D) in an individual with macrocephaly, ventricular dilatation, and features of VATER association (Reardon W et al. J Med Genet. 2001 Dec;38(12):820-3). This amino acid position is completely conserved on sequence alignment. 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: Nov 27, 2021

Support Center