NM_000548.5(TSC2):c.1377C>T (p.Gly459=) AND Tuberous sclerosis syndrome

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Sep 7, 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:: RCV000042409.10

Allele description [Variation Report for NM_000548.5(TSC2):c.1377C>T (p.Gly459=)]

NM_000548.5(TSC2):c.1377C>T (p.Gly459=)

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.1377C>T (p.Gly459=)

Other names:

p.G459G:GGC>GGT

HGVS:

NC_000016.10:g.2062987C>T
NG_005895.1:g.18682C>T
NM_000548.5:c.1377C>TMANE SELECT
NM_001077183.3:c.1377C>T
NM_001114382.3:c.1377C>T
NM_001318827.2:c.1266C>T
NM_001318829.2:c.1230C>T
NM_001318831.2:c.777C>T
NM_001318832.2:c.1410C>T
NM_001363528.2:c.1377C>T
NM_001370404.1:c.1377C>T
NM_001370405.1:c.1377C>T
NM_021055.3:c.1377C>T
NP_000539.2:p.Gly459=
NP_001070651.1:p.Gly459=
NP_001107854.1:p.Gly459=
NP_001305756.1:p.Gly422=
NP_001305758.1:p.Gly410=
NP_001305760.1:p.Gly259=
NP_001305761.1:p.Gly470=
NP_001350457.1:p.Gly459=
NP_001357333.1:p.Gly459=
NP_001357334.1:p.Gly459=
NP_066399.2:p.Gly459=
LRG_487t1:c.1377C>T
LRG_487:g.18682C>T
NC_000016.9:g.2112988C>T
NM_000548.3:c.1377C>T
NM_000548.4:c.1377C>T
p.G459G
p.Gly459Gly
p.(=)

Links:

Tuberous sclerosis database (TSC2): TSC2_00168; dbSNP: rs45517170

NCBI 1000 Genomes Browser:

rs45517170

Molecular consequence:

NM_000548.5:c.1377C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001077183.3:c.1377C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001114382.3:c.1377C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001318827.2:c.1266C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001318829.2:c.1230C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001318831.2:c.777C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001318832.2:c.1410C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001363528.2:c.1377C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001370404.1:c.1377C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001370405.1:c.1377C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_021055.3:c.1377C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Tuberous sclerosis syndrome (TSC)
Synonyms:: Tuberous sclerosis
Identifiers:: MONDO: MONDO:0001734; MedGen: C0041341; OMIM: PS191100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000066200	Tuberous sclerosis database (TSC2)	no classification provided (Tuberous Sclerosis Database Assertion Criteria 2015)	not provided	germline	curation	PubMed (2) [See all records that cite these PMIDs] 10205261, 17304050 Citation Link,
SCV000395579	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Apr 27, 2017)	germline	clinical testing	Citation Link,
SCV006060747	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Sep 7, 2022)	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

SCV000066200

Tuberous sclerosis database (TSC2)

no classification provided

(Tuberous Sclerosis Database Assertion Criteria 2015)

not provided

germline

curation

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

Citation Link,

SCV000395579

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Likely benign
(Apr 27, 2017)

germline

clinical testing

Citation Link,

SCV006060747

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Sep 7, 2022)

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	yes	2	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis.

Jones AC, Shyamsundar MM, Thomas MW, Maynard J, Idziaszczyk S, Tomkins S, Sampson JR, Cheadle JP.

Am J Hum Genet. 1999 May;64(5):1305-15. Review.

PubMed [citation]

PMID:: 10205261
PMCID:: PMC1377866

Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States.

Au KS, Williams AT, Roach ES, Batchelor L, Sparagana SP, Delgado MR, Wheless JW, Baumgartner JE, Roa BB, Wilson CM, Smith-Knuppel TK, Cheung MY, Whittemore VH, King TM, Northrup H.

Genet Med. 2007 Feb;9(2):88-100.

PubMed [citation]

PMID:: 17304050

See all PubMed Citations (3)

Details of each submission

From Tuberous sclerosis database (TSC2), SCV000066200.3

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

#	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 Illumina Laboratory Services, Illumina, SCV000395579.3

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

#	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 Color Diagnostics, LLC DBA Color Health, SCV006060747.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 25, 2025

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