U.S. flag

An official website of the United States government

NM_000368.5(TSC1):c.2446A>T (p.Lys816Ter) AND Tuberous sclerosis syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 27, 2018
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:
RCV000826206.4

Allele description [Variation Report for NM_000368.5(TSC1):c.2446A>T (p.Lys816Ter)]

NM_000368.5(TSC1):c.2446A>T (p.Lys816Ter)

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.2446A>T (p.Lys816Ter)
HGVS:
  • NC_000009.12:g.132901645T>A
  • NG_012386.1:g.47989A>T
  • NM_000368.5:c.2446A>TMANE SELECT
  • NM_001162426.2:c.2443A>T
  • NM_001162427.2:c.2293A>T
  • NM_001362177.2:c.2083A>T
  • NP_000359.1:p.Lys816Ter
  • NP_001155898.1:p.Lys815Ter
  • NP_001155899.1:p.Lys765Ter
  • NP_001349106.1:p.Lys695Ter
  • LRG_486t1:c.2446A>T
  • LRG_486:g.47989A>T
  • NC_000009.11:g.135777032T>A
  • NM_000368.4:c.2446A>T
  • p.Lys816X
Protein change:
K695*
Links:
dbSNP: rs1588299158
NCBI 1000 Genomes Browser:
rs1588299158
Molecular consequence:
  • NM_000368.5:c.2446A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001162426.2:c.2443A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001162427.2:c.2293A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001362177.2:c.2083A>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000967765Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Apr 27, 2018) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967765.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.Lys816X variant in TSC1 has been reported in one individual with tuberous sclerosis complex (TSC) in the tuberous sclerosis LOVD database (http://chromiu m.lovd.nl/LOVD2/TSC/home.php) and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 816, which is predicted to lead to a truncated or absent protein. Heterozygous loss of func tion of the TSC1 gene is an established disease mechanism in individuals with TS C. In summary, this variant meets criteria to be classified as pathogenic for tu berous sclerosis complex in an autosomal dominant manner based upon predicted im pact on the protein and absence in the general population. ACMG/AMP Criteria app lied: PVS1, PM2, PS4_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Dec 24, 2022