NM_000548.5(TSC2):c.4096G>T (p.Glu1366Ter) AND Tuberous sclerosis 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 7, 2021
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:: RCV000201169.5

Allele description [Variation Report for NM_000548.5(TSC2):c.4096G>T (p.Glu1366Ter)]

NM_000548.5(TSC2):c.4096G>T (p.Glu1366Ter)

Gene:

TSC2:TSC complex subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_000548.5(TSC2):c.4096G>T (p.Glu1366Ter)

HGVS:

NC_000016.10:g.2084318G>T
NG_005895.1:g.40013G>T
NM_000548.5:c.4096G>TMANE SELECT
NM_001077183.3:c.3895G>T
NM_001114382.3:c.4027G>T
NM_001318827.2:c.3787G>T
NM_001318829.2:c.3751G>T
NM_001318831.2:c.3364G>T
NM_001318832.2:c.3928G>T
NM_001363528.2:c.3898G>T
NM_001370404.1:c.3964G>T
NM_001370405.1:c.3967G>T
NM_021055.3:c.3967G>T
NP_000539.2:p.Glu1366Ter
NP_001070651.1:p.Glu1299Ter
NP_001107854.1:p.Glu1343Ter
NP_001305756.1:p.Glu1263Ter
NP_001305758.1:p.Glu1251Ter
NP_001305760.1:p.Glu1122Ter
NP_001305761.1:p.Glu1310Ter
NP_001350457.1:p.Glu1300Ter
NP_001357333.1:p.Glu1322Ter
NP_001357334.1:p.Glu1323Ter
NP_066399.2:p.Glu1323Ter
LRG_487t1:c.4096G>T
LRG_487:g.40013G>T
NC_000016.9:g.2134319G>T
NM_000548.3:c.4096G>T
p.(Glu1366*)

Protein change:

E1122*

Links:

Tuberous sclerosis database (TSC2): TSC2_00557; dbSNP: rs45517327

NCBI 1000 Genomes Browser:

rs45517327

Molecular consequence:

NM_000548.5:c.4096G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001077183.3:c.3895G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001114382.3:c.4027G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001318827.2:c.3787G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001318829.2:c.3751G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001318831.2:c.3364G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001318832.2:c.3928G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001363528.2:c.3898G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370404.1:c.3964G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370405.1:c.3967G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_021055.3:c.3967G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Tuberous sclerosis 2 (TSC2)
Identifiers:: MONDO: MONDO:0013199; MedGen: C1860707; Orphanet: 805; OMIM: 613254

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000255896	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Jan 17, 2013)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11112665, 26467025
SCV002040989	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000255896

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Jan 17, 2013)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002040989

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 7, 2021)

germline

clinical testing

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

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
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs.

Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J, Choy YS, Reeve MP, Thiele E, Egelhoff JC, Kasprzyk-Obara J, Domanska-Pakiela D, Kwiatkowski DJ.

Am J Hum Genet. 2001 Jan;68(1):64-80. Epub 2000 Dec 8.

PubMed [citation]

PMID:: 11112665
PMCID:: PMC1234935

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

See all PubMed Citations (3)

Details of each submission

From Athena Diagnostics, SCV000255896.2

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

#	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 Genome-Nilou Lab, SCV002040989.1

#	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

Last Updated: Jun 2, 2024

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