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NM_000368.5(TSC1):c.2356C>T (p.Arg786Ter) AND Tuberous sclerosis 1

Germline classification:
Pathogenic (5 submissions)
Last evaluated:
Oct 30, 2022
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:
RCV000201048.14

Allele description

NM_000368.5(TSC1):c.2356C>T (p.Arg786Ter)

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.2356C>T (p.Arg786Ter)
HGVS:
  • NC_000009.12:g.132902640G>A
  • NG_012386.1:g.46994C>T
  • NM_000368.5:c.2356C>TMANE SELECT
  • NM_001162426.2:c.2353C>T
  • NM_001162427.2:c.2203C>T
  • NM_001362177.2:c.1993C>T
  • NP_000359.1:p.Arg786Ter
  • NP_000359.1:p.Arg786Ter
  • NP_001155898.1:p.Arg785Ter
  • NP_001155899.1:p.Arg735Ter
  • NP_001349106.1:p.Arg665Ter
  • LRG_486t1:c.2356C>T
  • LRG_486:g.46994C>T
  • LRG_486p1:p.Arg786Ter
  • NC_000009.11:g.135778027G>A
  • NM_000368.3:c.2356C>T
  • NM_000368.4:c.2356C>T
  • p.R785X
  • p.(Arg786*)
  • p.Arg786*
Protein change:
R665*
Links:
Tuberous sclerosis database (TSC1): TSC1_00156; dbSNP: rs118203682
NCBI 1000 Genomes Browser:
rs118203682
Molecular consequence:
  • NM_000368.5:c.2356C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001162426.2:c.2353C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001162427.2:c.2203C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001362177.2:c.1993C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
2

Condition(s)

Name:
Tuberous sclerosis 1 (TSC1)
Identifiers:
MONDO: MONDO:0008612; MedGen: C1854465; Orphanet: 805; OMIM: 191100

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000552281Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Oct 30, 2022)
germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

SCV000782393Center for Human Genetics, Inc, Center for Human Genetics, Inc
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Nov 1, 2016)
germlineclinical testing

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

SCV001160789Cavalleri Lab, Royal College of Surgeons in Ireland
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Dec 11, 2019)
de novoresearch

PubMed (2)
[See all records that cite these PMIDs]

SCV001370505Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University
no assertion criteria provided
Pathogenic
(Jun 9, 2020)
germlineclinical testing

SCV002040775Genome-Nilou Lab
criteria provided, single submitter

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

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedde novoyesnot providednot providednot providednot providednot providedresearch
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
Japanesegermlineyes2not providednot providednot providednot providedclinical testing

Citations

PubMed

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

Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34.

van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S, Lindhout D, van den Ouweland A, Halley D, Young J, Burley M, Jeremiah S, Woodward K, Nahmias J, Fox M, Ekong R, Osborne J, Wolfe J, Povey S, Snell RG, Cheadle JP, Jones AC, et al.

Science. 1997 Aug 8;277(5327):805-8.

PubMed [citation]
PMID:
9242607
See all PubMed Citations (13)

Details of each submission

From Invitae, SCV000552281.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

This sequence change creates a premature translational stop signal (p.Arg786*) in the TSC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC1 are known to be pathogenic (PMID: 10227394, 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: 9242607, 9803264, 9863590, 9924605, 10227394, 10363127, 10533067, 11112665, 16981987). This variant is also known as 2577C>T. ClinVar contains an entry for this variant (Variation ID: 48943). For these reasons, this variant has been classified as Pathogenic.

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

From Center for Human Genetics, Inc, Center for Human Genetics, Inc, SCV000782393.1

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

From Cavalleri Lab, Royal College of Surgeons in Ireland, SCV001160789.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (2)

Description

ACMG evidence PVS1, PS2, PM2, PP5

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot providednot providednot providednot providednot provided

From Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, SCV001370505.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Japanese2not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not providednot providednot provided

From Genome-Nilou Lab, SCV002040775.1

#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: Dec 24, 2023