NM_000548.5(TSC2):c.5417_5418del (p.Phe1806fs) AND Tuberous sclerosis 2

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Feb 22, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV003850633.2

Allele description

NM_000548.5(TSC2):c.5417_5418del (p.Phe1806fs)

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.5417_5418del (p.Phe1806fs)

HGVS:

NC_000016.10:g.2088603_2088604del
NG_005895.1:g.44298_44299del
NG_008617.1:g.54618_54619del
NM_000548.5:c.5417_5418delMANE SELECT
NM_001077183.3:c.5216_5217del
NM_001114382.3:c.5348_5349del
NM_001318827.2:c.5108_5109del
NM_001318829.2:c.5072_5073del
NM_001318831.2:c.4685_4686del
NM_001318832.2:c.5249_5250del
NM_001363528.2:c.5219_5220del
NM_001370404.1:c.5285_5286del
NM_001370405.1:c.5276_5277del
NM_001406663.1:c.5414_5415del
NM_001406664.1:c.5345_5346del
NM_001406665.1:c.5339_5340del
NM_001406667.1:c.5309_5310del
NM_001406668.1:c.5306_5307del
NM_001406670.1:c.5237_5238del
NM_001406671.1:c.5207_5208del
NM_001406673.1:c.5204_5205del
NM_001406675.1:c.5201_5202del
NM_001406676.1:c.5198_5199del
NM_001406677.1:c.5159_5160del
NM_001406678.1:c.5105_5106del
NM_001406679.1:c.5069_5070del
NM_001406680.1:c.4817_4818del
NM_001406681.1:c.4757_4758del
NM_001406682.1:c.4748_4749del
NM_001406683.1:c.4748_4749del
NM_001406684.1:c.4745_4746del
NM_001406685.1:c.4619_4620del
NM_001406686.1:c.4619_4620del
NM_001406687.1:c.4616_4617del
NM_001406688.1:c.4616_4617del
NM_001406689.1:c.4004_4005del
NM_001406690.1:c.3944_3945del
NM_001406691.1:c.3941_3942del
NM_001406692.1:c.3875_3876del
NM_001406693.1:c.3875_3876del
NM_001406694.1:c.3875_3876del
NM_001406695.1:c.3872_3873del
NM_001406696.1:c.3872_3873del
NM_001406697.1:c.3872_3873del
NM_001406698.1:c.3614_3615del
NM_021055.3:c.5288_5289del
NP_000539.2:p.Phe1806Cysfs
NP_000539.2:p.Phe1806fs
NP_001070651.1:p.Phe1739fs
NP_001107854.1:p.Phe1783fs
NP_001305756.1:p.Phe1703fs
NP_001305758.1:p.Phe1691fs
NP_001305760.1:p.Phe1562fs
NP_001305761.1:p.Phe1750fs
NP_001350457.1:p.Phe1740fs
NP_001357333.1:p.Phe1762fs
NP_001357334.1:p.Phe1759fs
NP_001393592.1:p.Phe1805fs
NP_001393593.1:p.Phe1782fs
NP_001393594.1:p.Phe1780fs
NP_001393596.1:p.Phe1770fs
NP_001393597.1:p.Phe1769fs
NP_001393599.1:p.Phe1746fs
NP_001393600.1:p.Phe1736fs
NP_001393602.1:p.Phe1735fs
NP_001393604.1:p.Phe1734fs
NP_001393605.1:p.Phe1733fs
NP_001393606.1:p.Phe1720fs
NP_001393607.1:p.Phe1702fs
NP_001393608.1:p.Phe1690fs
NP_001393609.1:p.Phe1606fs
NP_001393610.1:p.Phe1586fs
NP_001393611.1:p.Phe1583fs
NP_001393612.1:p.Phe1583fs
NP_001393613.1:p.Phe1582fs
NP_001393614.1:p.Phe1540fs
NP_001393615.1:p.Phe1540fs
NP_001393616.1:p.Phe1539fs
NP_001393617.1:p.Phe1539fs
NP_001393618.1:p.Phe1335fs
NP_001393619.1:p.Phe1315fs
NP_001393620.1:p.Phe1314fs
NP_001393621.1:p.Phe1292fs
NP_001393622.1:p.Phe1292fs
NP_001393623.1:p.Phe1292fs
NP_001393624.1:p.Phe1291fs
NP_001393625.1:p.Phe1291fs
NP_001393626.1:p.Phe1291fs
NP_001393627.1:p.Phe1205fs
NP_066399.2:p.Phe1763fs
LRG_487t1:c.5417_5418del
LRG_487:g.44298_44299del
LRG_487p1:p.Phe1806Cysfs
NC_000016.9:g.2138603_2138604del
NC_000016.9:g.2138604_2138605del
NM_000548.3:c.5417_5418delTT
NR_176225.1:n.5369_5370del
NR_176226.1:n.5617_5618del
NR_176227.1:n.5545_5546del
NR_176228.1:n.5366_5367del
NR_176229.1:n.5291_5292del

Protein change:

F1205fs

Molecular consequence:

NM_000548.5:c.5417_5418del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001077183.3:c.5216_5217del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001114382.3:c.5348_5349del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318827.2:c.5108_5109del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318829.2:c.5072_5073del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318831.2:c.4685_4686del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318832.2:c.5249_5250del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363528.2:c.5219_5220del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370404.1:c.5285_5286del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370405.1:c.5276_5277del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406663.1:c.5414_5415del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406664.1:c.5345_5346del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406665.1:c.5339_5340del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406667.1:c.5309_5310del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406668.1:c.5306_5307del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406670.1:c.5237_5238del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406671.1:c.5207_5208del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406673.1:c.5204_5205del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406675.1:c.5201_5202del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406676.1:c.5198_5199del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406677.1:c.5159_5160del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406678.1:c.5105_5106del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406679.1:c.5069_5070del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406680.1:c.4817_4818del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406681.1:c.4757_4758del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406682.1:c.4748_4749del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406683.1:c.4748_4749del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406684.1:c.4745_4746del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406685.1:c.4619_4620del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406686.1:c.4619_4620del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406687.1:c.4616_4617del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406688.1:c.4616_4617del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406689.1:c.4004_4005del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406690.1:c.3944_3945del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406691.1:c.3941_3942del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406692.1:c.3875_3876del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406693.1:c.3875_3876del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406694.1:c.3875_3876del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406695.1:c.3872_3873del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406696.1:c.3872_3873del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406697.1:c.3872_3873del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406698.1:c.3614_3615del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_021055.3:c.5288_5289del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_176225.1:n.5369_5370del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176226.1:n.5617_5618del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176227.1:n.5545_5546del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176228.1:n.5366_5367del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176229.1:n.5291_5292del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

MAG: Planctomycetes bacterium RIFCSPLOWO2_12_FULL_50_35 rifcsplowo2_12_scaffold_...
MAG: Planctomycetes bacterium RIFCSPLOWO2_12_FULL_50_35 rifcsplowo2_12_scaffold_11173, whole genome shotgun sequence
gi|1088359699|gb|MHZB01000005.1||gn :MHZB01|rifcsplowo2_12_scaffold_11173

Nucleotide
MAG: Planctomycetes bacterium RIFCSPLOWO2_12_FULL_50_35 rifcsplowo2_12_scaffold_...
MAG: Planctomycetes bacterium RIFCSPLOWO2_12_FULL_50_35 rifcsplowo2_12_scaffold_15702, whole genome shotgun sequence
gi|1088359363|gb|MHZB01000018.1||gn :MHZB01|rifcsplowo2_12_scaffold_15702

Nucleotide
MAG: Planctomycetes bacterium RIFCSPLOWO2_12_FULL_50_35 rifcsplowo2_12_scaffold_...
MAG: Planctomycetes bacterium RIFCSPLOWO2_12_FULL_50_35 rifcsplowo2_12_scaffold_1332, whole genome shotgun sequence
gi|1088359583|gb|MHZB01000009.1||gn :MHZB01|rifcsplowo2_12_scaffold_1332

Nucleotide
MAG: Planctomycetes bacterium RIFCSPLOWO2_12_FULL_50_35 rifcsplowo2_12_scaffold_...
MAG: Planctomycetes bacterium RIFCSPLOWO2_12_FULL_50_35 rifcsplowo2_12_scaffold_10399, whole genome shotgun sequence
gi|1088359750|gb|MHZB01000003.1||gn :MHZB01|rifcsplowo2_12_scaffold_10399

Nucleotide
LOC105187020 [Harpegnathos saltator]
LOC105187020 [Harpegnathos saltator]
Gene ID:105187020

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004654861	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 3, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11781698, 28492532
SCV004930815	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Feb 22, 2024)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23389244, 27859028, 11781698 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004654861

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 3, 2022)

germline

clinical testing

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

SCV004930815

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely pathogenic
(Feb 22, 2024)

unknown

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Mutational analysis of TSC1 and TSC2 in Japanese patients with tuberous sclerosis complex revealed higher incidence of TSC1 patients than previously reported.

Niida Y, Wakisaka A, Tsuji T, Yamada H, Kuroda M, Mitani Y, Okumura A, Yokoi A.

J Hum Genet. 2013 Apr;58(4):216-25. doi: 10.1038/jhg.2013.3. Epub 2013 Feb 7.

PubMed [citation]

PMID:: 23389244

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004654861.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the C-terminus of the TSC2 protein. Other variant(s) that disrupt this region (p.*1808Argext*?) have been observed in individuals with TSC2-related conditions (PMID: 11781698; Invitae). This suggests that this may be a clinically significant region of the protein. This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the TSC2 gene (p.Phe1806Cysfs*?). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2 amino acid(s) of the TSC2 protein and extend the protein by an uncertain number of additional amino acid residues.

#	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

From Myriad Genetics, Inc., SCV004930815.1

#	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 considered likely pathogenic. This variant creates a frameshift predicted to result in the incorporation of abnormal amino acid sequence into the protein product and abnormal protein elongation. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 11781698, 23389244, 27859028]. Functional studies indicate this variant impacts protein function [PMID: 11781698].

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

Last Updated: May 7, 2024

ClinVar

Relating variation to medicine