NM_000314.8(PTEN):c.1104T>C (p.Asp368=) AND not specified

Germline classification:: Benign (4 submissions)
Last evaluated:: Mar 9, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000153792.19

Allele description [Variation Report for NM_000314.8(PTEN):c.1104T>C (p.Asp368=)]

NM_000314.8(PTEN):c.1104T>C (p.Asp368=)

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.1104T>C (p.Asp368=)

Other names:

p.D368D:GAT>GAC; NM_000314.6(PTEN):c.1104T>C(p.Asp368=)

HGVS:

NC_000010.11:g.87965364T>C
NG_007466.2:g.106926T>C
NM_000314.8:c.1104T>CMANE SELECT
NM_001304717.5:c.1623T>C
NM_001304718.2:c.513T>C
NP_000305.3:p.Asp368=
NP_001291646.4:p.Asp541=
NP_001291647.1:p.Asp171=
LRG_311t1:c.1104T>C
LRG_311:g.106926T>C
NC_000010.10:g.89725121T>C
NM_000314.4:c.1104T>C
NM_000314.6:c.1104T>C
NP_000305.3:p.(=)
p.Asp368Asp
p.D368D

Links:

dbSNP: rs35979531

NCBI 1000 Genomes Browser:

rs35979531

Molecular consequence:

NM_000314.8:c.1104T>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001304717.5:c.1623T>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001304718.2:c.513T>C - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000171227	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Jun 30, 2014)	germline	clinical testing	Citation Link,
SCV000203370	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Benign (Dec 17, 2013)	germline	clinical testing	Citation Link,
SCV000303569	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001361386	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Mar 9, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25669429, 9788441 Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

KLLN epigenotype-phenotype associations in Cowden syndrome.

Nizialek EA, Mester JL, Dhiman VK, Smiraglia DJ, Eng C.

Eur J Hum Genet. 2015 Nov;23(11):1538-43. doi: 10.1038/ejhg.2015.8. Epub 2015 Feb 11.

PubMed [citation]

PMID:: 25669429
PMCID:: PMC4613489

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000171227.11

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Eurofins Ntd Llc (ga), SCV000203370.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	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		1	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV000303569.1

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

#	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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361386.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: PTEN c.1104T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00057 in 265518 control chromosomes, predominantly at a frequency of 0.0057 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 912 fold of the estimated maximal expected allele frequency for a pathogenic variant in PTEN causing Cowden Syndrome phenotype (6.3e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. The variant was also detected in the FLOSSIES database in 26 African American women who are cancer free and older than age 70, providing further supporting evidence for a benign role. However, these observations need to be cautiously considered due to the potential of the PTEN pseudogene being captured at this site. c.1104T>C has been reported in the literature in one Cowden Syndrome study but it was unclear if found in patients or controls (Nizialek_2015) and in one individual with prostate cancer (Dong_1998). These reports do not provide unequivocal conclusions about association of the variant with Cowden Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submissions from clinical diagnostic laboratories and reputable databases (evaluation after 2014) cite the variant as likely benign (4x) and once as benign. Based on the evidence outlined above, the variant was classified as benign.

#	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: May 1, 2024

ClinVar

Relating variation to medicine