NM_000548.5(TSC2):c.1819G>A (p.Ala607Thr) AND Tuberous sclerosis syndrome

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Jan 13, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000054869.9

Allele description [Variation Report for NM_000548.5(TSC2):c.1819G>A (p.Ala607Thr)]

NM_000548.5(TSC2):c.1819G>A (p.Ala607Thr)

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.1819G>A (p.Ala607Thr)

Other names:

p.A607T:GCG>ACG

HGVS:

NC_000016.10:g.2070558G>A
NG_005895.1:g.26253G>A
NM_000548.5:c.1819G>AMANE SELECT
NM_001077183.3:c.1819G>A
NM_001114382.3:c.1819G>A
NM_001318827.2:c.1708G>A
NM_001318829.2:c.1672G>A
NM_001318831.2:c.1219G>A
NM_001318832.2:c.1852G>A
NM_001363528.2:c.1819G>A
NM_001370404.1:c.1819G>A
NM_001370405.1:c.1819G>A
NM_021055.3:c.1819G>A
NP_000539.2:p.Ala607Thr
NP_001070651.1:p.Ala607Thr
NP_001107854.1:p.Ala607Thr
NP_001305756.1:p.Ala570Thr
NP_001305758.1:p.Ala558Thr
NP_001305760.1:p.Ala407Thr
NP_001305761.1:p.Ala618Thr
NP_001350457.1:p.Ala607Thr
NP_001357333.1:p.Ala607Thr
NP_001357334.1:p.Ala607Thr
NP_066399.2:p.Ala607Thr
LRG_487t1:c.1819G>A
LRG_487:g.26253G>A
NC_000016.9:g.2120559G>A
NM_000548.3:c.1819G>A
NM_000548.4:c.1819G>A
P49815:p.Ala607Thr
p.A607T
p.(Ala607Thr)

Protein change:

A407T

Links:

Tuberous sclerosis database (TSC2): TSC2_00008; UniProtKB: P49815#VAR_005649; dbSNP: rs45517203

NCBI 1000 Genomes Browser:

rs45517203

Molecular consequence:

NM_000548.5:c.1819G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.1819G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.1819G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.1708G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.1672G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.1219G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.1852G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.1819G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.1819G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.1819G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.1819G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000067238	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] 15024740, 21309039 Citation Link,
SCV000395591	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Jan 13, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000067238

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,

SCV000395591

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Likely benign
(Jan 13, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	4	not provided	not provided	not provided	not provided	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel TSC2 mutations and decreased expression of tuberin in cultured tumor cells with an insertion mutation.

Feng JH, Yamamoto T, Nanba E, Ninomiya H, Oka A, Ohno K.

Hum Mutat. 2004 Apr;23(4):397.

PubMed [citation]

PMID:: 15024740

Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex.

Hoogeveen-Westerveld M, Wentink M, van den Heuvel D, Mozaffari M, Ekong R, Povey S, den Dunnen JT, Metcalfe K, Vallee S, Krueger S, Bergoffen J, Shashi V, Elmslie F, Kwiatkowski D, Sampson J, Vidales C, Dzarir J, Garcia-Planells J, Dies K, Maat-Kievit A, van den Ouweland A, Halley D, et al.

Hum Mutat. 2011 Apr;32(4):424-35. doi: 10.1002/humu.21451. Epub 2011 Mar 8.

PubMed [citation]

PMID:: 21309039

Details of each submission

From Tuberous sclerosis database (TSC2), SCV000067238.3

#	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, SCV000395591.3

#	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely 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

Last Updated: Oct 20, 2024

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