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NM_000314.8(PTEN):c.1212A>T (p.Ter404Cys) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 3, 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:
RCV000214783.4

Allele description [Variation Report for NM_000314.8(PTEN):c.1212A>T (p.Ter404Cys)]

NM_000314.8(PTEN):c.1212A>T (p.Ter404Cys)

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.1212A>T (p.Ter404Cys)
Other names:
*404C; *577C; *207C
HGVS:
  • NC_000010.11:g.87965472A>T
  • NG_007466.2:g.107034A>T
  • NM_000314.8:c.1212A>TMANE SELECT
  • NM_001304717.5:c.1731A>T
  • NM_001304718.2:c.621A>T
  • NP_000305.3:p.Ter404Cys
  • NP_001291646.4:p.Ter577Cys
  • NP_001291647.1:p.Ter207Cys
  • LRG_311t1:c.1212A>T
  • LRG_311:g.107034A>T
  • NC_000010.10:g.89725229A>T
  • NC_000010.10:g.89725229A>T
  • NM_000314.4:c.1212A>T
  • NM_000314.7(PTEN):c.1212A>T
  • p.Ter404Cys
Links:
dbSNP: rs876660879
NCBI 1000 Genomes Browser:
rs876660879
Molecular consequence:
  • NM_000314.8:c.1212A>T - stop lost - [Sequence Ontology: SO:0001578]
  • NM_001304717.5:c.1731A>T - stop lost - [Sequence Ontology: SO:0001578]
  • NM_001304718.2:c.621A>T - stop lost - [Sequence Ontology: SO:0001578]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000278659Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Oct 3, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases.

Valiente M, Andrés-Pons A, Gomar B, Torres J, Gil A, Tapparel C, Antonarakis SE, Pulido R.

J Biol Chem. 2005 Aug 12;280(32):28936-43. Epub 2005 Jun 10.

PubMed [citation]
PMID:
15951562

Disruption of epithelial architecture caused by loss of PTEN or by oncogenic mutant p110α/PIK3CA but not by HER2 or mutant AKT1.

Berglund FM, Weerasinghe NR, Davidson L, Lim JC, Eickholt BJ, Leslie NR.

Oncogene. 2013 Sep 12;32(37):4417-26. doi: 10.1038/onc.2012.459. Epub 2012 Oct 22.

PubMed [citation]
PMID:
23085752
PMCID:
PMC3648380
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000278659.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The c.1212A>T pathogenic mutation (also known as p.*404Cext*8), located in coding exon 9 of the PTEN gene, results from an A to T substitution at nucleotide position 1212, which is the last nucleotide of the PTEN gene. The stop codon at position 404 is replaced by cysteine, resulting in an elongation of the protein by 8 amino acids. This variant has been determined to be the result of a de novo mutation or germline mosaicism in one individual with PTEN hamartoma tumor syndrome (PHTS, external laboratory communication). In addition, this alteration has been observed in multiple individuals with a personal and/or family history that is consistent with PHTS (Busch RM et al. Transl Psychiatry, 2019 Oct;9:253; Ambry internal data). Based on internal structural analysis, this elongation is anticipated to result in a significant decrease in structural flexibility to the PDZ motif on the C- terminus (Valiente M et al. J Biol Chem, 2005 Aug;280:28936-43, Ambry internal data). This termination codon is highly conserved in available vertebrate species. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: May 7, 2024