NM_000314.8(PTEN):c.1066A>G (p.Asn356Asp) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 30, 2022
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:: RCV001818323.5

Allele description [Variation Report for NM_000314.8(PTEN):c.1066A>G (p.Asn356Asp)]

NM_000314.8(PTEN):c.1066A>G (p.Asn356Asp)

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.1066A>G (p.Asn356Asp)

HGVS:

NC_000010.11:g.87965326A>G
NG_007466.2:g.106888A>G
NM_000314.8:c.1066A>GMANE SELECT
NM_001304717.5:c.1585A>G
NM_001304718.2:c.475A>G
NP_000305.3:p.Asn356Asp
NP_001291646.4:p.Asn529Asp
NP_001291647.1:p.Asn159Asp
LRG_311t1:c.1066A>G
LRG_311:g.106888A>G
NC_000010.10:g.89725083A>G
NM_000314.4:c.1066A>G
NM_000314.6:c.1066A>G
p.N356D

Protein change:

N159D

Links:

dbSNP: rs587782345

NCBI 1000 Genomes Browser:

rs587782345

Molecular consequence:

NM_000314.8:c.1066A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001304717.5:c.1585A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001304718.2:c.475A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

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cerebral cavernous malformations 2 protein isoform 1 [Homo sapiens]
cerebral cavernous malformations 2 protein isoform 1 [Homo sapiens]
gi|71067341|ref|NP_001025006.1|

Protein
Mus musculus inhibitor of growth family, member 1 (Ing1), mRNA
Mus musculus inhibitor of growth family, member 1 (Ing1), mRNA
gi|6754349|ref|NM_011919.1|

Nucleotide
Gabarapl1 GABA type A receptor associated protein like 1 [Mus musculus]
Gabarapl1 GABA type A receptor associated protein like 1 [Mus musculus]
Gene ID:57436

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002070087	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 13, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002600820	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Oct 30, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21343951, 21194675, 28152038, 29706350 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002070087

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 13, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002600820

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Oct 30, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	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

Analysis of prevalence and degree of macrocephaly in patients with germline PTEN mutations and of brain weight in Pten knock-in murine model.

Mester JL, Tilot AK, Rybicki LA, Frazier TW 2nd, Eng C.

Eur J Hum Genet. 2011 Jul;19(7):763-8. doi: 10.1038/ejhg.2011.20. Epub 2011 Feb 23.

PubMed [citation]

PMID:: 21343951
PMCID:: PMC3137495

See all PubMed Citations (5)

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV002070087.1

#	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	no	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, SCV002600820.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Variant summary: PTEN c.1066A>G (p.Asn356Asp) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 245272 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1066A>G has been reported in the literature multiple times from the same group, indicating it occurs in at least one individual affected with Cowden Syndrome (Mester_2011, Tan_2011, Ngeow_2011, Nizialek_2015). These data do not allow any conclusion about variant significance. At least one publication using a yeast assay to evaluate the impact of the variant on lipid phosphatase activity showed the variant had "wild-type like activity" (Michell_2018). Four ClinVar submitters have assessed the variant since 2014: all four classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: Sep 29, 2024

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