NM_000314.8(PTEN):c.1184A>G (p.Asp395Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 18, 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:: RCV002337706.2

Allele description [Variation Report for NM_000314.8(PTEN):c.1184A>G (p.Asp395Gly)]

NM_000314.8(PTEN):c.1184A>G (p.Asp395Gly)

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.1184A>G (p.Asp395Gly)

HGVS:

NC_000010.11:g.87965444A>G
NG_007466.2:g.107006A>G
NM_000314.8:c.1184A>GMANE SELECT
NM_001304717.5:c.1703A>G
NM_001304718.2:c.593A>G
NP_000305.3:p.Asp395Gly
NP_000305.3:p.Asp395Gly
NP_001291646.4:p.Asp568Gly
NP_001291647.1:p.Asp198Gly
LRG_311t1:c.1184A>G
LRG_311:g.107006A>G
LRG_311p1:p.Asp395Gly
NC_000010.10:g.89725201A>G
NM_000314.4:c.1184A>G

Protein change:

D198G

Molecular consequence:

NM_000314.8:c.1184A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001304717.5:c.1703A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001304718.2:c.593A>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002638652	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jul 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002638652

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jul 18, 2022)

germline

clinical testing

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

Citation Link

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

Multiplex assessment of protein variant abundance by massively parallel sequencing.

Matreyek KA, Starita LM, Stephany JJ, Martin B, Chiasson MA, Gray VE, Kircher M, Khechaduri A, Dines JN, Hause RJ, Bhatia S, Evans WE, Relling MV, Yang W, Shendure J, Fowler DM.

Nat Genet. 2018 Jun;50(6):874-882. doi: 10.1038/s41588-018-0122-z. Epub 2018 May 21.

PubMed [citation]

PMID:: 29785012
PMCID:: PMC5980760

Details of each submission

From Ambry Genetics, SCV002638652.2

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

Description

The p.D395G variant (also known as c.1184A>G), located in coding exon 9 of the PTEN gene, results from an A to G substitution at nucleotide position 1184. The aspartic acid at codon 395 is replaced by glycine, an amino acid with similar properties. This variant demonstrated wild type-like intracellular protein abundance on one multiplex functional assay (Matreyek KA et al. Nat Genet, 2018 06;50:874-882). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). This amino acid position is well conserved in available vertebrate species. In addition, as a missense substitution this is predicted to be inconclusive by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

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