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NM_000548.5(TSC2):c.4662+1G>C AND Tuberous sclerosis 2

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 6, 2020
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:
RCV001065003.2

Allele description [Variation Report for NM_000548.5(TSC2):c.4662+1G>C]

NM_000548.5(TSC2):c.4662+1G>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.4662+1G>C
HGVS:
  • NC_000016.10:g.2085323G>C
  • NG_005895.1:g.41018G>C
  • NM_000548.5:c.4662+1G>CMANE SELECT
  • NM_001077183.3:c.4461+1G>C
  • NM_001114382.3:c.4593+1G>C
  • NM_001318827.2:c.4353+1G>C
  • NM_001318829.2:c.4317+1G>C
  • NM_001318831.2:c.3930+1G>C
  • NM_001318832.2:c.4494+1G>C
  • NM_001363528.2:c.4464+1G>C
  • NM_001370404.1:c.4530+1G>C
  • NM_001370405.1:c.4533+1G>C
  • NM_001406663.1:c.4659+1G>C
  • NM_001406664.1:c.4590+1G>C
  • NM_001406665.1:c.4584+1G>C
  • NM_001406667.1:c.4554+1G>C
  • NM_001406668.1:c.4551+1G>C
  • NM_001406670.1:c.4482+1G>C
  • NM_001406671.1:c.4452+1G>C
  • NM_001406673.1:c.4449+1G>C
  • NM_001406675.1:c.4446+1G>C
  • NM_001406676.1:c.4443+1G>C
  • NM_001406677.1:c.4404+1G>C
  • NM_001406678.1:c.4350+1G>C
  • NM_001406679.1:c.4314+1G>C
  • NM_001406680.1:c.4062+1G>C
  • NM_001406681.1:c.4002+1G>C
  • NM_001406682.1:c.3993+1G>C
  • NM_001406683.1:c.3993+1G>C
  • NM_001406684.1:c.3990+1G>C
  • NM_001406685.1:c.3864+1G>C
  • NM_001406686.1:c.3864+1G>C
  • NM_001406687.1:c.3861+1G>C
  • NM_001406688.1:c.3861+1G>C
  • NM_001406689.1:c.3249+1G>C
  • NM_001406690.1:c.3189+1G>C
  • NM_001406691.1:c.3186+1G>C
  • NM_001406692.1:c.3120+1G>C
  • NM_001406693.1:c.3120+1G>C
  • NM_001406694.1:c.3120+1G>C
  • NM_001406695.1:c.3117+1G>C
  • NM_001406696.1:c.3117+1G>C
  • NM_001406697.1:c.3117+1G>C
  • NM_001406698.1:c.2859+1G>C
  • NM_021055.3:c.4533+1G>C
  • LRG_487t1:c.4662+1G>C
  • LRG_487:g.41018G>C
  • NC_000016.9:g.2135324G>C
  • NM_000548.3:c.4662+1G>C
Links:
dbSNP: rs45514095
NCBI 1000 Genomes Browser:
rs45514095
Molecular consequence:
  • NM_000548.5:c.4662+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001077183.3:c.4461+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001114382.3:c.4593+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001318827.2:c.4353+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001318829.2:c.4317+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001318831.2:c.3930+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001318832.2:c.4494+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001363528.2:c.4464+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001370404.1:c.4530+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001370405.1:c.4533+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406663.1:c.4659+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406664.1:c.4590+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406665.1:c.4584+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406667.1:c.4554+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406668.1:c.4551+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406670.1:c.4482+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406671.1:c.4452+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406673.1:c.4449+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406675.1:c.4446+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406676.1:c.4443+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406677.1:c.4404+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406678.1:c.4350+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406679.1:c.4314+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406680.1:c.4062+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406681.1:c.4002+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406682.1:c.3993+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406683.1:c.3993+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406684.1:c.3990+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406685.1:c.3864+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406686.1:c.3864+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406687.1:c.3861+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406688.1:c.3861+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406689.1:c.3249+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406690.1:c.3189+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406691.1:c.3186+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406692.1:c.3120+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406693.1:c.3120+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406694.1:c.3120+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406695.1:c.3117+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406696.1:c.3117+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406697.1:c.3117+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406698.1:c.2859+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_021055.3:c.4533+1G>C - 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
SCV001229941Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jan 6, 2020) 		germlineclinical testing

PubMed (4)
[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

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, SCV001229941.1

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

Description

This sequence change affects a donor splice site in intron 36 of the TSC2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of tuberous sclerosis complex (PMID: 27859028). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Sep 29, 2024