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NM_000314.8(PTEN):c.1010T>C (p.Phe337Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 6, 2022
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:
RCV002322690.2

Allele description [Variation Report for NM_000314.8(PTEN):c.1010T>C (p.Phe337Ser)]

NM_000314.8(PTEN):c.1010T>C (p.Phe337Ser)

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.1010T>C (p.Phe337Ser)
HGVS:
  • NC_000010.11:g.87961102T>C
  • NG_007466.2:g.102664T>C
  • NM_000314.8:c.1010T>CMANE SELECT
  • NM_001304717.5:c.1529T>C
  • NM_001304718.2:c.419T>C
  • NP_000305.3:p.Phe337Ser
  • NP_000305.3:p.Phe337Ser
  • NP_001291646.4:p.Phe510Ser
  • NP_001291647.1:p.Phe140Ser
  • LRG_311t1:c.1010T>C
  • LRG_311:g.102664T>C
  • LRG_311p1:p.Phe337Ser
  • NC_000010.10:g.89720859T>C
  • NM_000314.4:c.1010T>C
Protein change:
F140S
Molecular consequence:
  • NM_000314.8:c.1010T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001304717.5:c.1529T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001304718.2:c.419T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002609273Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(May 6, 2022) 		germlineclinical testing

PubMed (4)
[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

Cowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers.

Lachlan KL, Lucassen AM, Bunyan D, Temple IK.

J Med Genet. 2007 Sep;44(9):579-85. Epub 2007 May 25.

PubMed [citation]
PMID:
17526800
PMCID:
PMC2597943

Conformational stability and catalytic activity of PTEN variants linked to cancers and autism spectrum disorders.

Johnston SB, Raines RT.

Biochemistry. 2015 Feb 24;54(7):1576-82. doi: 10.1021/acs.biochem.5b00028. Epub 2015 Feb 13.

PubMed [citation]
PMID:
25647146
PMCID:
PMC4372197
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002609273.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The p.F337S variant (also known as c.1010T>C), located in coding exon 8 of the PTEN gene, results from a T to C substitution at nucleotide position 1010. The phenylalanine at codon 337 is replaced by serine, an amino acid with highly dissimilar properties. This variant has been seen in one proband satisfying clinical diagnostic criteria for PTEN Hamartoma Tumor syndrome (Lachlan KL et al. J. Med. Genet., 2007 Sep;44:579-85). A conformational stability study using transformed bacterial cells showed this variant decreased protein stability and function (Johnston SB et al. Biochemistry, 2015 Feb;54:1576-82). In a cultured human cell-line, this variant demonstrated loss of protein abundance (Matreyek KA et al. Nat. Genet., 2018 06;50:874-882). However, in a humanized yeast model, lipid phosphatase activity for this variant is similar to normal cell function (Mighell TL et al. Am. J. Hum. Genet., 2018 05;102:943-955). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: May 1, 2024