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NM_000548.5(TSC2):c.138_138+1del AND Tuberous sclerosis 2

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Nov 7, 2021
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:
RCV001056624.6

Allele description [Variation Report for NM_000548.5(TSC2):c.138_138+1del]

NM_000548.5(TSC2):c.138_138+1del

Gene:
TSC2:TSC complex subunit 2 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_000548.5(TSC2):c.138_138+1del
HGVS:
  • NC_000016.10:g.2048751AG[1]
  • NG_005895.1:g.4446AG[1]
  • NG_008412.1:g.4114TC[1]
  • NM_000548.5:c.138_138+1delMANE SELECT
  • NM_001077183.3:c.138_138+1del
  • NM_001114382.3:c.138_138+1del
  • NM_001318827.2:c.138_138+1del
  • NM_001318829.2:c.-10+688_-10+689del
  • NM_001318831.2:c.-89_-89+1del
  • NM_001318832.2:c.171_171+1del
  • NM_001363528.2:c.138_138+1del
  • NM_001370404.1:c.138_138+1del
  • NM_001370405.1:c.138_138+1del
  • NM_021055.3:c.138_138+1del
  • LRG_487t1:c.138_138+1del2
  • LRG_1366:g.4114TC[1]
  • LRG_487:g.4446AG[1]
  • NC_000016.9:g.2098751_2098752del
  • NC_000016.9:g.2098752AG[1]
  • NM_000548.3:c.138_138+1del2
  • NM_000548.3:c.138_138+1delAG
  • p.?
Links:
Tuberous sclerosis database (TSC2): TSC2_00796; dbSNP: rs137854117
NCBI 1000 Genomes Browser:
rs137854117
Molecular consequence:
  • NM_001318829.2:c.-10+688_-10+689del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000548.5:c.138_138+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001077183.3:c.138_138+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001114382.3:c.138_138+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001318827.2:c.138_138+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001318831.2:c.-89_-89+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001318832.2:c.171_171+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001363528.2:c.138_138+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001370404.1:c.138_138+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001370405.1:c.138_138+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_021055.3:c.138_138+1del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Tuberous sclerosis 2 (TSC2)
Identifiers:
MONDO: MONDO:0013199; MedGen: C1860707; Orphanet: 805; OMIM: 613254

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001221077Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 1, 2019) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002040909Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Nov 7, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

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
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001221077.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). For these reasons, this variant has been classified as Pathogenic. Disruption of this splice site has been observed in several individuals affected with tuberous sclerosis (PMID: 15595939, 25782670, 8990012, 9829910). ClinVar contains an entry for this variant (Variation ID: 49675). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 2 of the TSC2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Genome-Nilou Lab, SCV002040909.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 14, 2024