NM_000548.5(TSC2):c.268C>T (p.Gln90Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 20, 2023
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:: RCV000381969.10

Allele description [Variation Report for NM_000548.5(TSC2):c.268C>T (p.Gln90Ter)]

NM_000548.5(TSC2):c.268C>T (p.Gln90Ter)

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.268C>T (p.Gln90Ter)

HGVS:

NC_000016.10:g.2053384C>T
NG_005895.1:g.9079C>T
NM_000548.5:c.268C>TMANE SELECT
NM_001077183.3:c.268C>T
NM_001114382.3:c.268C>T
NM_001318827.2:c.226-912C>T
NM_001318829.2:c.121C>T
NM_001318831.2:c.-1-2812C>T
NM_001318832.2:c.301C>T
NM_001363528.2:c.268C>T
NM_001370404.1:c.268C>T
NM_001370405.1:c.268C>T
NM_021055.3:c.268C>T
NP_000539.2:p.Gln90Ter
NP_001070651.1:p.Gln90Ter
NP_001107854.1:p.Gln90Ter
NP_001305758.1:p.Gln41Ter
NP_001305761.1:p.Gln101Ter
NP_001350457.1:p.Gln90Ter
NP_001357333.1:p.Gln90Ter
NP_001357334.1:p.Gln90Ter
NP_066399.2:p.Gln90Ter
LRG_487t1:c.268C>T
LRG_487:g.9079C>T
NC_000016.9:g.2103385C>T
NM_000548.3:c.268C>T
p.Gln90*
p.(Gln90*)

Protein change:

Q101*

Links:

Tuberous sclerosis database (TSC2): TSC2_00036; dbSNP: rs45517099

NCBI 1000 Genomes Browser:

rs45517099

Molecular consequence:

NM_001318827.2:c.226-912C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001318831.2:c.-1-2812C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000548.5:c.268C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001077183.3:c.268C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001114382.3:c.268C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001318829.2:c.121C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001318832.2:c.301C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001363528.2:c.268C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370404.1:c.268C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370405.1:c.268C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_021055.3:c.268C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000329780	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 20, 2023)	germline	clinical testing	Citation Link,
SCV000615894	Athena Diagnostics Inc	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Jul 31, 2017)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 10735580, 11112665, 16981987, 12111193, 17304050, 15798777, 25782670, 20498439, 20633017, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000329780

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jan 20, 2023)

germline

clinical testing

Citation Link,

SCV000615894

Athena Diagnostics Inc

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Jul 31, 2017)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Superiority of denaturing high performance liquid chromatography over single-stranded conformation and conformation-sensitive gel electrophoresis for mutation detection in TSC2.

Choy YS, Dabora SL, Hall F, Ramesh V, Niida Y, Franz D, Kasprzyk-Obara J, Reeve MP, Kwiatkowski DJ.

Ann Hum Genet. 1999 Sep;63(Pt 5):383-91.

PubMed [citation]

PMID:: 10735580

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

See all PubMed Citations (10)

Details of each submission

From GeneDx, SCV000329780.7

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

Description

Identified in patients with tuberous sclerosis complex referred for genetic testing at GeneDx and in published literature (Choy 1999, Au 2007); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10735580, 25525159, 12111193, 16981987, 11112665, 25782670, 20633017, 17536269, 15798777, 20498439, 17304050, 32211034)

#	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 Athena Diagnostics Inc, SCV000615894.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

#	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: Feb 20, 2024

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