NM_000548.5(TSC2):c.41del (p.Lys14fs) AND Tuberous sclerosis 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 9, 2019
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:: RCV001214238.5

Allele description [Variation Report for NM_000548.5(TSC2):c.41del (p.Lys14fs)]

NM_000548.5(TSC2):c.41del (p.Lys14fs)

Gene:

TSC2:TSC complex subunit 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_000548.5(TSC2):c.41del (p.Lys14fs)

HGVS:

NC_000016.10:g.2048656del
NG_005895.1:g.4351del
NG_008412.1:g.4212del
NM_000548.5:c.41delMANE SELECT
NM_001077183.3:c.41del
NM_001114382.3:c.41del
NM_001318827.2:c.41del
NM_001318829.2:c.-10+591del
NM_001318831.2:c.-186del
NM_001318832.2:c.74del
NM_001363528.2:c.41del
NM_001370404.1:c.41del
NM_001370405.1:c.41del
NM_021055.3:c.41del
NP_000539.2:p.Lys14fs
NP_001070651.1:p.Lys14fs
NP_001107854.1:p.Lys14fs
NP_001305756.1:p.Lys14fs
NP_001305761.1:p.Lys25fs
NP_001350457.1:p.Lys14fs
NP_001357333.1:p.Lys14fs
NP_001357334.1:p.Lys14fs
NP_066399.2:p.Lys14fs
LRG_487t1:c.41del
LRG_1366:g.4212del
LRG_487:g.4351del
NC_000016.9:g.2098656del
NC_000016.9:g.2098657del
NM_000548.3:c.41del

Protein change:

K14fs

Links:

dbSNP: rs2084674122

NCBI 1000 Genomes Browser:

rs2084674122

Molecular consequence:

NM_001318831.2:c.-186del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000548.5:c.41del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001077183.3:c.41del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001114382.3:c.41del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318827.2:c.41del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318832.2:c.74del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363528.2:c.41del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370404.1:c.41del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370405.1:c.41del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_021055.3:c.41del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318829.2:c.-10+591del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Tuberous sclerosis 2 (TSC2)
Identifiers:: MONDO: MONDO:0013199; MedGen: C1860707; Orphanet: 805; OMIM: 613254

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001385911	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 9, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10205261, 17304050, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001385911

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 9, 2019)

germline

clinical testing

PubMed (3)
[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

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 (3)

Details of each submission

From Invitae, SCV001385911.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys14Serfs*32) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with TSC2-related conditions. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050).

#	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 20, 2024

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