NM_000314.8(PTEN):c.371G>A (p.Cys124Tyr) AND PTEN hamartoma tumor syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 17, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000471590.5

Allele description [Variation Report for NM_000314.8(PTEN):c.371G>A (p.Cys124Tyr)]

NM_000314.8(PTEN):c.371G>A (p.Cys124Tyr)

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.371G>A (p.Cys124Tyr)

HGVS:

NC_000010.11:g.87933130G>A
NG_007466.2:g.74692G>A
NM_000314.8:c.371G>AMANE SELECT
NM_001304717.5:c.890G>A
NM_001304718.2:c.-380G>A
NP_000305.3:p.Cys124Tyr
NP_001291646.4:p.Cys297Tyr
LRG_311t1:c.371G>A
LRG_311:g.74692G>A
NC_000010.10:g.89692887G>A
NM_000314.4:c.371G>A

Protein change:

C124Y

Links:

dbSNP: rs876660535

NCBI 1000 Genomes Browser:

rs876660535

Molecular consequence:

NM_001304718.2:c.-380G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000314.8:c.371G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001304717.5:c.890G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: PTEN hamartoma tumor syndrome (PHTS)
Synonyms:: PTEN Hamartomatous Tumour Syndrome; PTEN-related disorders
Identifiers:: MONDO: MONDO:0017623; MeSH: D006223; MedGen: C1959582

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000541631	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 17, 2023)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 15211648, 31970404, 10555148, 12938083, 17324556, 20685300, 21194675, 21828076, 25647146, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000541631

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 17, 2023)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Two novel mutations of PTEN gene in Japanese patients with Cowden syndrome.

Sawada T, Okada T, Miwa K, Satoh H, Asano A, Mabuchi H.

Am J Med Genet A. 2004 Jul 1;128A(1):12-4.

PubMed [citation]

PMID:: 15211648

Germline cancer predisposition variants and pediatric glioma: a population-based study in California.

Muskens IS, de Smith AJ, Zhang C, Hansen HM, Morimoto L, Metayer C, Ma X, Walsh KM, Wiemels JL.

Neuro Oncol. 2020 Jun 9;22(6):864-874. doi: 10.1093/neuonc/noaa014.

PubMed [citation]

PMID:: 31970404
PMCID:: PMC7283023

See all PubMed Citations (10)

Details of each submission

From Invitae, SCV000541631.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 124 of the PTEN protein (p.Cys124Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with anaplastic astrocytoma and/or Cowden syndrome (PMID: 15211648, 31970404). ClinVar contains an entry for this variant (Variation ID: 233631). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is expected to disrupt PTEN function. This variant disrupts the p.Cys124 amino acid residue in PTEN. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10555148, 12938083, 17324556, 20685300, 21194675, 21828076, 25647146). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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