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NM_000548.5(TSC2):c.337-2A>C AND Tuberous sclerosis 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 17, 2023
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:
RCV003038865.2

Allele description [Variation Report for NM_000548.5(TSC2):c.337-2A>C]

NM_000548.5(TSC2):c.337-2A>C

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.337-2A>C
HGVS:
  • NC_000016.10:g.2054294A>C
  • NG_005895.1:g.9989A>C
  • NM_000548.5:c.337-2A>CMANE SELECT
  • NM_001077183.3:c.337-2A>C
  • NM_001114382.3:c.337-2A>C
  • NM_001318827.2:c.226-2A>C
  • NM_001318829.2:c.190-2A>C
  • NM_001318831.2:c.-1-1902A>C
  • NM_001318832.2:c.370-2A>C
  • NM_001363528.2:c.337-2A>C
  • NM_001370404.1:c.337-2A>C
  • NM_001370405.1:c.337-2A>C
  • NM_001406663.1:c.337-2A>C
  • NM_001406664.1:c.337-2A>C
  • NM_001406665.1:c.337-2A>C
  • NM_001406667.1:c.427-2A>C
  • NM_001406668.1:c.427-2A>C
  • NM_001406670.1:c.226-2A>C
  • NM_001406671.1:c.337-2A>C
  • NM_001406673.1:c.337-2A>C
  • NM_001406675.1:c.190-2A>C
  • NM_001406676.1:c.190-2A>C
  • NM_001406677.1:c.280-2A>C
  • NM_001406678.1:c.226-2A>C
  • NM_001406679.1:c.190-2A>C
  • NM_001406680.1:c.-480-2A>C
  • NM_001406681.1:c.-109-2A>C
  • NM_001406682.1:c.-1-1902A>C
  • NM_001406683.1:c.-480-2A>C
  • NM_001406684.1:c.-1-1902A>C
  • NM_001406685.1:c.-1-1902A>C
  • NM_001406686.1:c.-1-1902A>C
  • NM_001406687.1:c.-480-2A>C
  • NM_001406688.1:c.-1-1902A>C
  • NM_001406689.1:c.-1095-2A>C
  • NM_001406690.1:c.-1095-2A>C
  • NM_001406691.1:c.-1095-2A>C
  • NM_001406692.1:c.-1095-2A>C
  • NM_001406693.1:c.-1311-2A>C
  • NM_001406694.1:c.-976-2A>C
  • NM_001406695.1:c.-976-2A>C
  • NM_001406696.1:c.-1083-2A>C
  • NM_001406697.1:c.-1095-2A>C
  • NM_001406698.1:c.-1271-2A>C
  • NM_021055.3:c.337-2A>C
  • LRG_487:g.9989A>C
  • NC_000016.9:g.2104295A>C
Molecular consequence:
  • NM_001318831.2:c.-1-1902A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406682.1:c.-1-1902A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406684.1:c.-1-1902A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406685.1:c.-1-1902A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406686.1:c.-1-1902A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406688.1:c.-1-1902A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000548.5:c.337-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001077183.3:c.337-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001114382.3:c.337-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001318827.2:c.226-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001318829.2:c.190-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001318832.2:c.370-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001363528.2:c.337-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001370404.1:c.337-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001370405.1:c.337-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406663.1:c.337-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406664.1:c.337-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406665.1:c.337-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406667.1:c.427-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406668.1:c.427-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406670.1:c.226-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406671.1:c.337-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406673.1:c.337-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406675.1:c.190-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406676.1:c.190-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406677.1:c.280-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406678.1:c.226-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406679.1:c.190-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406680.1:c.-480-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406681.1:c.-109-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406683.1:c.-480-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406687.1:c.-480-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406689.1:c.-1095-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406690.1:c.-1095-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406691.1:c.-1095-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406692.1:c.-1095-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406693.1:c.-1311-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406694.1:c.-976-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406695.1:c.-976-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406696.1:c.-1083-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406697.1:c.-1095-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406698.1:c.-1271-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_021055.3:c.337-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV003335080Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Mar 17, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Superiority of denaturing high performance liquid chromatography over single-stranded conformation and conformation-sensitive gel electrophoresis for mutation detection in TSC2.

Choy YS, Dabora SL, Hall F, Ramesh V, Niida Y, Franz D, Kasprzyk-Obara J, Reeve MP, Kwiatkowski DJ.

Ann Hum Genet. 1999 Sep;63(Pt 5):383-91.

PubMed [citation]
PMID:
10735580

Mutational analysis of TSC1 and TSC2 in Japanese patients with tuberous sclerosis complex revealed higher incidence of TSC1 patients than previously reported.

Niida Y, Wakisaka A, Tsuji T, Yamada H, Kuroda M, Mitani Y, Okumura A, Yokoi A.

J Hum Genet. 2013 Apr;58(4):216-25. doi: 10.1038/jhg.2013.3. Epub 2013 Feb 7.

PubMed [citation]
PMID:
23389244
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV003335080.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2113612). Disruption of this splice site has been observed in individuals with tuberous sclerosis complex (PMID: 10735580, 23389244, 27406250). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 4 of the TSC2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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).

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

Last Updated: Feb 28, 2024