NM_000368.5(TSC1):c.2341C>T (p.Gln781Ter) AND Tuberous sclerosis 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 7, 2024
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:: RCV000473593.6

Allele description [Variation Report for NM_000368.5(TSC1):c.2341C>T (p.Gln781Ter)]

NM_000368.5(TSC1):c.2341C>T (p.Gln781Ter)

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.2341C>T (p.Gln781Ter)

HGVS:

NC_000009.12:g.132902655G>A
NG_012386.1:g.46979C>T
NM_000368.5:c.2341C>TMANE SELECT
NM_001162426.2:c.2338C>T
NM_001162427.2:c.2188C>T
NM_001362177.2:c.1978C>T
NP_000359.1:p.Gln781Ter
NP_000359.1:p.Gln781Ter
NP_001155898.1:p.Gln780Ter
NP_001155899.1:p.Gln730Ter
NP_001349106.1:p.Gln660Ter
LRG_486t1:c.2341C>T
LRG_486:g.46979C>T
LRG_486p1:p.Gln781Ter
NC_000009.11:g.135778042G>A
NM_000368.3:c.2341C>T
NM_000368.4:c.2341C>T
p.(Gln781*)

Protein change:

Q660*

Links:

Tuberous sclerosis database (TSC1): TSC1_00155; dbSNP: rs118203680

NCBI 1000 Genomes Browser:

rs118203680

Molecular consequence:

NM_000368.5:c.2341C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001162426.2:c.2338C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001162427.2:c.2188C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001362177.2:c.1978C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000552248	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 7, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10227394, 17304050, 29500070, 32313033, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000552248

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 7, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation.

van Slegtenhorst M, Verhoef S, Tempelaars A, Bakker L, Wang Q, Wessels M, Bakker R, Nellist M, Lindhout D, Halley D, van den Ouweland A.

J Med Genet. 1999 Apr;36(4):285-9.

PubMed [citation]

PMID:: 10227394
PMCID:: PMC1734341

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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000552248.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Gln781*) 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 individuals with tuberous sclerosis complex (PMID: 29500070, 32313033). ClinVar contains an entry for this variant (Variation ID: 48941). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 25, 2025

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