NM_000548.5(TSC2):c.5034C>G (p.Tyr1678Ter) AND Tuberous sclerosis 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 30, 2022
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:: RCV000795199.6

Allele description [Variation Report for NM_000548.5(TSC2):c.5034C>G (p.Tyr1678Ter)]

NM_000548.5(TSC2):c.5034C>G (p.Tyr1678Ter)

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.5034C>G (p.Tyr1678Ter)

HGVS:

NC_000016.10:g.2087907C>G
NG_005895.1:g.43602C>G
NG_008617.1:g.55314G>C
NM_000548.5:c.5034C>GMANE SELECT
NM_001077183.3:c.4833C>G
NM_001114382.3:c.4965C>G
NM_001318827.2:c.4725C>G
NM_001318829.2:c.4689C>G
NM_001318831.2:c.4302C>G
NM_001318832.2:c.4866C>G
NM_001363528.2:c.4836C>G
NM_001370404.1:c.4902C>G
NM_001370405.1:c.4905C>G
NM_021055.3:c.4905C>G
NP_000539.2:p.Tyr1678Ter
NP_001070651.1:p.Tyr1611Ter
NP_001107854.1:p.Tyr1655Ter
NP_001305756.1:p.Tyr1575Ter
NP_001305758.1:p.Tyr1563Ter
NP_001305760.1:p.Tyr1434Ter
NP_001305761.1:p.Tyr1622Ter
NP_001350457.1:p.Tyr1612Ter
NP_001357333.1:p.Tyr1634Ter
NP_001357334.1:p.Tyr1635Ter
NP_066399.2:p.Tyr1635Ter
LRG_487t1:c.5034C>G
LRG_487:g.43602C>G
NC_000016.9:g.2137908C>G
NM_000548.3:c.5034C>G
p.(Tyr1678*)

Protein change:

Y1434*

Links:

Tuberous sclerosis database (TSC2): TSC2_00633; dbSNP: rs45467993

NCBI 1000 Genomes Browser:

rs45467993

Molecular consequence:

NM_000548.5:c.5034C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001077183.3:c.4833C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001114382.3:c.4965C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001318827.2:c.4725C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001318829.2:c.4689C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001318831.2:c.4302C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001318832.2:c.4866C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001363528.2:c.4836C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001370404.1:c.4902C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001370405.1:c.4905C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_021055.3:c.4905C>G - 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
SCV000934643	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 30, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10205261, 17304050, 15595939, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000934643

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 30, 2022)

germline

clinical testing

PubMed (4)
[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

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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000934643.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Tyr1678*) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with tuberous sclerosis complex (PMID: 15595939). ClinVar contains an entry for this variant (Variation ID: 49852). For these reasons, this variant has been classified as Pathogenic.

#	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: Jun 29, 2025

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