NM_000314.8(PTEN):c.737C>T (p.Pro246Leu) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Feb 22, 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:: RCV000212883.34

Allele description [Variation Report for NM_000314.8(PTEN):c.737C>T (p.Pro246Leu)]

NM_000314.8(PTEN):c.737C>T (p.Pro246Leu)

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.737C>T (p.Pro246Leu)

Other names:

p.P246L:CCG>CTG; NM_000314.6(PTEN):c.737C>T(p.Pro246Leu)

HGVS:

NC_000010.11:g.87957955C>T
NG_007466.2:g.99517C>T
NM_000314.8:c.737C>TMANE SELECT
NM_001304717.5:c.1256C>T
NM_001304718.2:c.146C>T
NP_000305.3:p.Pro246Leu
NP_001291646.4:p.Pro419Leu
NP_001291647.1:p.Pro49Leu
LRG_311t1:c.737C>T
LRG_311:g.99517C>T
NC_000010.10:g.89717712C>T
NM_000314.4:c.737C>T
NM_000314.5:c.737C>T
NM_000314.6:c.737C>T
P60484:p.Pro246Leu
p.P246L

Protein change:

P246L

Links:

UniProtKB: P60484#VAR_008740; dbSNP: rs587782350

NCBI 1000 Genomes Browser:

rs587782350

Molecular consequence:

NM_000314.8:c.737C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001304717.5:c.1256C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001304718.2:c.146C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Canis lupus familiaris endothelin 3 (EDN3), mRNA
Canis lupus familiaris endothelin 3 (EDN3), mRNA
gi|50950152|ref|NM_001002942.1|

Nucleotide
PREDICTED: Canis lupus familiaris glycoprotein nmb (GPNMB), transcript variant X...
PREDICTED: Canis lupus familiaris glycoprotein nmb (GPNMB), transcript variant X5, mRNA
gi|1952684944|ref|XM_539472.7|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000222227	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 22, 2022)	germline	clinical testing	Citation Link,
SCV001249163	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jul 1, 2019)	germline	clinical testing	Citation Link,
SCV001447049	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002024766	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 16, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	1	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

Details of each submission

From GeneDx, SCV000222227.13

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

Description

Observed in multiple unrelated patients with features of PTEN Hamartoma Tumor syndrome referred for genetic testing at GeneDx and in published literature (Marsh 1999, Zhou 2003, Hobert 2012, Vanderver 2014); Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies suggest a damaging effect: partial loss of phosphastase activity and protein instability (Andres-Pons 2007, Rodriguez-Escudero 2011, Mighell 2018, Matreyek 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27477328, 10923032, 26681312, 10076877, 17942903, 25669429, 23934111, 12938083, 21194675, 14566704, 25527629, 23161105, 14518068, 24744697, 22261759, 24375884, 10400993, 15805158, 27146902, 30555518, 28152038, 28263302, 30174244, 31336731, 31046523, 21828076, 29706350, 31447099, 32162695, 33726816, 18626510)

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001249163.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	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	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001447049.1

#	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	yes	1	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002024766.3

#	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

Last Updated: Oct 20, 2024

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