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NM_000368.5(TSC1):c.2818C>T (p.Gln940Ter) AND Tuberous sclerosis syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 10, 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:
RCV002307655.1

Allele description [Variation Report for NM_000368.5(TSC1):c.2818C>T (p.Gln940Ter)]

NM_000368.5(TSC1):c.2818C>T (p.Gln940Ter)

Gene:
TSC1:TSC complex subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.13
Genomic location:
Preferred name:
NM_000368.5(TSC1):c.2818C>T (p.Gln940Ter)
HGVS:
  • NC_000009.12:g.132897341G>A
  • NG_012386.1:g.52293C>T
  • NM_000368.5:c.2818C>TMANE SELECT
  • NM_001162426.2:c.2815C>T
  • NM_001162427.2:c.2665C>T
  • NM_001362177.2:c.2455C>T
  • NP_000359.1:p.Gln940Ter
  • NP_001155898.1:p.Gln939Ter
  • NP_001155899.1:p.Gln889Ter
  • NP_001349106.1:p.Gln819Ter
  • LRG_486t1:c.2818C>T
  • LRG_486:g.52293C>T
  • NC_000009.11:g.135772728G>A
  • NC_000009.11:g.135772728G>A
  • NM_000368.4:c.2818C>T
Protein change:
Q819*
Links:
dbSNP: rs1588290078
NCBI 1000 Genomes Browser:
rs1588290078
Molecular consequence:
  • NM_000368.5:c.2818C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001162426.2:c.2815C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001162427.2:c.2665C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001362177.2:c.2455C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Tuberous sclerosis syndrome (TSC)
Synonyms:
Tuberous sclerosis
Identifiers:
MONDO: MONDO:0001734; MedGen: C0041341; OMIM: PS191100

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002600396Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Oct 10, 2022) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

TSC2 pathogenic variants are predictive of severe clinical manifestations in TSC infants: results of the EPISTOP study.

Ogórek B, Hamieh L, Hulshof HM, Lasseter K, Klonowska K, Kuijf H, Moavero R, Hertzberg C, Weschke B, Riney K, Feucht M, Scholl T, Krsek P, Nabbout R, Jansen AC, Benova B, Aronica E, Lagae L, Curatolo P, Borkowska J, Sadowski K, Domańska-Pakieła D, et al.

Genet Med. 2020 Sep;22(9):1489-1497. doi: 10.1038/s41436-020-0823-4. Epub 2020 May 28.

PubMed [citation]
PMID:
32461669

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002600396.1

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

Description

Variant summary: TSC1 c.2818C>T (p.Gln940X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251452 control chromosomes. c.2818C>T has been reported in the literature in individuals affected with Tuberous Sclerosis Complex (Ogrek_2020). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=3) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Jun 2, 2024