NM_000548.5(TSC2):c.5397G>C (p.Ser1799=) AND Tuberous sclerosis syndrome

Germline classification:: Benign (3 submissions)
Last evaluated:: Feb 5, 2024
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:: RCV000043113.18

Allele description [Variation Report for NM_000548.5(TSC2):c.5397G>C (p.Ser1799=)]

NM_000548.5(TSC2):c.5397G>C (p.Ser1799=)

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.5397G>C (p.Ser1799=)

HGVS:

NC_000016.10:g.2088583G>C
NG_005895.1:g.44278G>C
NG_008617.1:g.54638C>G
NM_000548.5:c.5397G>CMANE SELECT
NM_001077183.3:c.5196G>C
NM_001114382.3:c.5328G>C
NM_001318827.2:c.5088G>C
NM_001318829.2:c.5052G>C
NM_001318831.2:c.4665G>C
NM_001318832.2:c.5229G>C
NM_001363528.2:c.5199G>C
NM_001370404.1:c.5265G>C
NM_001370405.1:c.5256G>C
NM_021055.3:c.5268G>C
NP_000539.2:p.Ser1799=
NP_001070651.1:p.Ser1732=
NP_001107854.1:p.Ser1776=
NP_001305756.1:p.Ser1696=
NP_001305758.1:p.Ser1684=
NP_001305760.1:p.Ser1555=
NP_001305761.1:p.Ser1743=
NP_001350457.1:p.Ser1733=
NP_001357333.1:p.Ser1755=
NP_001357334.1:p.Ser1752=
NP_066399.2:p.Ser1756=
LRG_487t1:c.5397G>C
LRG_487:g.44278G>C
NC_000016.9:g.2138584G>C
NM_000548.3:c.5397G>C
NM_000548.4:c.5397G>C
p.S1799S
p.Ser1799Ser
p.(=)

Links:

Tuberous sclerosis database (TSC2): TSC2_00002; dbSNP: rs1051771

NCBI 1000 Genomes Browser:

rs1051771

Molecular consequence:

NM_000548.5:c.5397G>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001077183.3:c.5196G>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001114382.3:c.5328G>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001318827.2:c.5088G>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001318829.2:c.5052G>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001318831.2:c.4665G>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001318832.2:c.5229G>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001363528.2:c.5199G>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001370404.1:c.5265G>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001370405.1:c.5256G>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_021055.3:c.5268G>C - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

16089

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
SCV000066912	Tuberous sclerosis database (TSC2)	no classification provided (Tuberous Sclerosis Database Assertion Criteria 2015)	not provided	germline	curation	PubMed (7) [See all records that cite these PMIDs] 10533067, 12111193, 12136241, 15595939, 16114042, 17304050, 8824881 Citation Link,
SCV000395687	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Jan 12, 2018)	germline	clinical testing	Citation Link,
SCV004817519	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Feb 5, 2024)	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

SCV000066912

Tuberous sclerosis database (TSC2)

no classification provided

(Tuberous Sclerosis Database Assertion Criteria 2015)

not provided

germline

curation

PubMed (7)
[See all records that cite these PMIDs]

Citation Link,

SCV000395687

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Jan 12, 2018)

germline

clinical testing

Citation Link,

SCV004817519

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Feb 5, 2024)

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	no	1	not provided	not provided	not provided	not provided	curation
not provided	germline	yes	9	not provided	not provided	not provided	not provided	curation
not provided	germline	unknown	16089	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis.

Niida Y, Lawrence-Smith N, Banwell A, Hammer E, Lewis J, Beauchamp RL, Sims K, Ramesh V, Ozelius L.

Hum Mutat. 1999;14(5):412-22.

PubMed [citation]

PMID:: 10533067

TSC1 and TSC2 mutations in tuberous sclerosis, the associated phenotypes and a model to explain observed TSC1/ TSC2 frequency ratios.

Langkau N, Martin N, Brandt R, Zügge K, Quast S, Wiegele G, Jauch A, Rehm M, Kuhl A, Mack-Vetter M, Zimmerhackl LB, Janssen B.

Eur J Pediatr. 2002 Jul;161(7):393-402. Epub 2002 Jun 8.

PubMed [citation]

PMID:: 12111193

See all PubMed Citations (8)

Details of each submission

From Tuberous sclerosis database (TSC2), SCV000066912.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (7)
2	not provided	not provided	not provided	not provided	curation	PubMed (7)

Description

Unaffected

#	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
2	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV000395687.3

#	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 in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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 All of Us Research Program, National Institutes of Health, SCV004817519.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	16089	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	108544	not provided	not provided		16089	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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