Incidental Mutation 'R7522:Tsc2'
ID 582757
Institutional Source Beutler Lab
Gene Symbol Tsc2
Ensembl Gene ENSMUSG00000002496
Gene Name TSC complex subunit 2
Synonyms tuberin, Nafld, tuberous sclerosis 2
MMRRC Submission 045594-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7522 (G1)
Quality Score 225.009
Status Validated
Chromosome 17
Chromosomal Location 24814790-24851604 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 24849939 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Asparagine at position 58 (I58N)
Ref Sequence ENSEMBL: ENSMUSP00000094986 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000047611] [ENSMUST00000097373] [ENSMUST00000226284] [ENSMUST00000226398] [ENSMUST00000227509] [ENSMUST00000227607] [ENSMUST00000227745] [ENSMUST00000228412]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000047611
SMART Domains Protein: ENSMUSP00000047413
Gene: ENSMUSG00000041429

DomainStartEndE-ValueType
low complexity region 9 20 N/A INTRINSIC
low complexity region 24 37 N/A INTRINSIC
low complexity region 55 68 N/A INTRINSIC
ENDO3c 126 276 1.06e-58 SMART
FES 277 297 4.82e-3 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000097373
AA Change: I58N

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000094986
Gene: ENSMUSG00000002496
AA Change: I58N

DomainStartEndE-ValueType
Pfam:DUF3384 54 470 4e-103 PFAM
Pfam:Tuberin 555 903 5.9e-149 PFAM
low complexity region 1023 1054 N/A INTRINSIC
low complexity region 1271 1278 N/A INTRINSIC
low complexity region 1310 1328 N/A INTRINSIC
low complexity region 1330 1344 N/A INTRINSIC
low complexity region 1378 1398 N/A INTRINSIC
Pfam:Rap_GAP 1497 1685 1.3e-43 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000226284
AA Change: I58N

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
Predicted Effect probably damaging
Transcript: ENSMUST00000226398
AA Change: I58N

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
Predicted Effect probably benign
Transcript: ENSMUST00000227509
Predicted Effect probably benign
Transcript: ENSMUST00000227607
Predicted Effect possibly damaging
Transcript: ENSMUST00000227745
AA Change: I58N

PolyPhen 2 Score 0.740 (Sensitivity: 0.85; Specificity: 0.92)
Predicted Effect possibly damaging
Transcript: ENSMUST00000228412
AA Change: I58N

PolyPhen 2 Score 0.558 (Sensitivity: 0.88; Specificity: 0.91)
Meta Mutation Damage Score 0.9319 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.8%
  • 20x: 99.3%
Validation Efficiency 97% (75/77)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Mutations in this gene lead to tuberous sclerosis complex. Its gene product is believed to be a tumor suppressor and is able to stimulate specific GTPases. The protein associates with hamartin in a cytosolic complex, possibly acting as a chaperone for hamartin. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous null mutants exhibit liver hypoplasia, open neural tube, thickened myocardium and die by embryonic day 9.5-12.5. Heterozygotes develop renal cystadenomas, liver hemangiomas (sometimes resulting in fatal bleeding) and lung adenomas. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 76 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A030014E15Rik G T 1: 82,902,949 (GRCm39) C82F unknown Het
Adam21 G C 12: 81,605,722 (GRCm39) T680R possibly damaging Het
Adgrf4 A C 17: 42,980,675 (GRCm39) Y137D probably benign Het
Ago3 T C 4: 126,257,600 (GRCm39) K477R probably benign Het
Ahnak T A 19: 8,979,686 (GRCm39) D323E probably benign Het
Amph A G 13: 19,270,715 (GRCm39) D108G probably damaging Het
Ankrd10 A T 8: 11,682,910 (GRCm39) C106S probably damaging Het
Bmp5 A T 9: 75,683,384 (GRCm39) T4S probably benign Het
Brix1 G A 15: 10,476,676 (GRCm39) R267C probably damaging Het
Calcrl G A 2: 84,203,708 (GRCm39) S24L probably benign Het
Ccdc40 T G 11: 119,123,047 (GRCm39) I213R possibly damaging Het
Cd300lg A G 11: 101,945,028 (GRCm39) I413V probably benign Het
Cdh3 G A 8: 107,268,005 (GRCm39) D347N probably damaging Het
Clcn3 T C 8: 61,394,446 (GRCm39) T55A probably benign Het
Cnga4 A G 7: 105,055,195 (GRCm39) T260A probably damaging Het
Cpne8 G T 15: 90,486,022 (GRCm39) P147Q probably benign Het
Cpsf6 A G 10: 117,203,734 (GRCm39) Y74H unknown Het
Cryl1 A T 14: 57,513,428 (GRCm39) S264R probably benign Het
Cyp39a1 C T 17: 43,978,370 (GRCm39) probably benign Het
Cyp4f39 T C 17: 32,705,946 (GRCm39) S346P probably damaging Het
Cyria A G 12: 12,408,057 (GRCm39) T28A possibly damaging Het
Ddhd1 G A 14: 45,895,104 (GRCm39) A122V possibly damaging Het
Dnmt1 C A 9: 20,831,498 (GRCm39) C662F probably damaging Het
E2f6 G A 12: 16,872,125 (GRCm39) G190S probably benign Het
Esp34 A T 17: 38,870,432 (GRCm39) I109F possibly damaging Het
Espl1 A T 15: 102,213,486 (GRCm39) D604V probably damaging Het
Exo1 T C 1: 175,728,870 (GRCm39) C645R probably benign Het
Fah A G 7: 84,246,282 (GRCm39) V189A probably benign Het
Fam184b A C 5: 45,688,093 (GRCm39) Y939D probably damaging Het
Fchsd2 T A 7: 100,908,829 (GRCm39) L410* probably null Het
Gak A T 5: 108,739,065 (GRCm39) I665N possibly damaging Het
Galnt9 A G 5: 110,743,705 (GRCm39) probably null Het
Gcg T C 2: 62,306,103 (GRCm39) R165G probably benign Het
Hexd T C 11: 121,108,923 (GRCm39) V214A possibly damaging Het
Hoxb3 A T 11: 96,235,507 (GRCm39) S145C probably damaging Het
Il18 A G 9: 50,486,640 (GRCm39) Y23C probably damaging Het
Itgav A T 2: 83,632,373 (GRCm39) I954F probably benign Het
Kcna4 A G 2: 107,126,600 (GRCm39) R445G probably damaging Het
Kyat3 T A 3: 142,440,305 (GRCm39) L343Q probably damaging Het
Lgals4 A T 7: 28,537,117 (GRCm39) D139V possibly damaging Het
Lrp3 C T 7: 34,903,755 (GRCm39) G197D probably damaging Het
Lyst T A 13: 13,821,668 (GRCm39) C1347* probably null Het
Man2a2 G C 7: 80,018,613 (GRCm39) A82G probably benign Het
Map3k4 T C 17: 12,480,219 (GRCm39) Q661R probably benign Het
Marcks A C 10: 37,012,577 (GRCm39) F153V unknown Het
Mocs1 T C 17: 49,742,292 (GRCm39) probably null Het
Naa60 A G 16: 3,719,768 (GRCm39) T232A probably benign Het
Oosp1 A T 19: 11,666,065 (GRCm39) I75N probably benign Het
Opn3 A G 1: 175,493,189 (GRCm39) V125A probably benign Het
Or2ag18 A G 7: 106,404,994 (GRCm39) V225A probably damaging Het
Or2f1 T A 6: 42,721,568 (GRCm39) I199N probably damaging Het
Or4c102 A G 2: 88,423,005 (GRCm39) T286A possibly damaging Het
Or7g27 T A 9: 19,250,294 (GRCm39) C179* probably null Het
Palb2 T C 7: 121,712,501 (GRCm39) T947A probably damaging Het
Pde5a C T 3: 122,634,648 (GRCm39) R730* probably null Het
Plcl1 T C 1: 55,735,523 (GRCm39) I288T probably benign Het
Plxnb2 A G 15: 89,045,977 (GRCm39) I966T probably benign Het
Prkcz T C 4: 155,355,742 (GRCm39) E400G probably damaging Het
Prpf8 A G 11: 75,400,102 (GRCm39) D2332G possibly damaging Het
Ptgds T G 2: 25,357,920 (GRCm39) T154P probably benign Het
Rel T C 11: 23,720,676 (GRCm39) probably null Het
Rxylt1 A G 10: 121,917,344 (GRCm39) W390R probably damaging Het
Serpinb1c T A 13: 33,066,200 (GRCm39) K248N probably benign Het
Shkbp1 A C 7: 27,046,583 (GRCm39) W394G possibly damaging Het
Slc47a2 A G 11: 61,193,076 (GRCm39) V559A probably benign Het
Sox6 A T 7: 115,400,813 (GRCm39) F10I probably damaging Het
Stkld1 T C 2: 26,837,259 (GRCm39) V303A probably benign Het
Styk1 T A 6: 131,289,803 (GRCm39) probably null Het
Tet1 T C 10: 62,654,762 (GRCm39) T1574A possibly damaging Het
Tkt A T 14: 30,290,180 (GRCm39) I270F possibly damaging Het
Trak1 A G 9: 121,271,777 (GRCm39) E166G probably damaging Het
Uhmk1 T A 1: 170,042,809 (GRCm39) M1L probably benign Het
Usp50 T C 2: 126,625,146 (GRCm39) Y21C probably damaging Het
Vmn1r180 C G 7: 23,652,685 (GRCm39) P283A probably damaging Het
Vmn1r83 A G 7: 12,055,505 (GRCm39) M184T possibly damaging Het
Vmn2r109 A G 17: 20,774,665 (GRCm39) I230T probably benign Het
Other mutations in Tsc2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00231:Tsc2 APN 17 24,827,081 (GRCm39) missense probably damaging 1.00
IGL00985:Tsc2 APN 17 24,816,105 (GRCm39) missense probably damaging 1.00
IGL01386:Tsc2 APN 17 24,832,259 (GRCm39) missense probably damaging 1.00
IGL01468:Tsc2 APN 17 24,840,071 (GRCm39) missense possibly damaging 0.90
IGL01530:Tsc2 APN 17 24,841,636 (GRCm39) missense possibly damaging 0.76
IGL02390:Tsc2 APN 17 24,819,427 (GRCm39) missense probably damaging 1.00
IGL02398:Tsc2 APN 17 24,840,703 (GRCm39) missense probably damaging 1.00
IGL02741:Tsc2 APN 17 24,848,943 (GRCm39) missense probably damaging 1.00
IGL03191:Tsc2 APN 17 24,847,028 (GRCm39) missense probably damaging 1.00
IGL03372:Tsc2 APN 17 24,838,444 (GRCm39) missense probably damaging 1.00
IGL03412:Tsc2 APN 17 24,816,042 (GRCm39) missense probably damaging 0.98
Twitch UTSW 17 24,815,716 (GRCm39) splice site probably null
PIT4515001:Tsc2 UTSW 17 24,840,121 (GRCm39) missense probably benign 0.15
R0025:Tsc2 UTSW 17 24,849,978 (GRCm39) splice site probably benign
R0025:Tsc2 UTSW 17 24,849,978 (GRCm39) splice site probably benign
R0138:Tsc2 UTSW 17 24,818,600 (GRCm39) missense possibly damaging 0.65
R0540:Tsc2 UTSW 17 24,840,686 (GRCm39) missense probably damaging 1.00
R0570:Tsc2 UTSW 17 24,845,701 (GRCm39) missense probably damaging 1.00
R0607:Tsc2 UTSW 17 24,840,686 (GRCm39) missense probably damaging 1.00
R0826:Tsc2 UTSW 17 24,815,932 (GRCm39) missense probably benign 0.04
R1430:Tsc2 UTSW 17 24,817,997 (GRCm39) critical splice donor site probably null
R1440:Tsc2 UTSW 17 24,833,366 (GRCm39) missense probably damaging 1.00
R1466:Tsc2 UTSW 17 24,827,947 (GRCm39) missense probably damaging 1.00
R1466:Tsc2 UTSW 17 24,827,947 (GRCm39) missense probably damaging 1.00
R1541:Tsc2 UTSW 17 24,850,950 (GRCm39) missense probably damaging 1.00
R1717:Tsc2 UTSW 17 24,816,042 (GRCm39) missense probably damaging 0.98
R1799:Tsc2 UTSW 17 24,823,382 (GRCm39) missense probably benign
R2030:Tsc2 UTSW 17 24,842,444 (GRCm39) splice site probably benign
R2147:Tsc2 UTSW 17 24,840,116 (GRCm39) missense possibly damaging 0.62
R2888:Tsc2 UTSW 17 24,850,969 (GRCm39) critical splice donor site probably null
R3609:Tsc2 UTSW 17 24,841,524 (GRCm39) missense possibly damaging 0.74
R3610:Tsc2 UTSW 17 24,841,524 (GRCm39) missense possibly damaging 0.74
R3811:Tsc2 UTSW 17 24,848,011 (GRCm39) missense probably benign 0.09
R3895:Tsc2 UTSW 17 24,818,786 (GRCm39) missense probably damaging 1.00
R3962:Tsc2 UTSW 17 24,840,140 (GRCm39) splice site probably benign
R3971:Tsc2 UTSW 17 24,842,562 (GRCm39) missense probably damaging 1.00
R4018:Tsc2 UTSW 17 24,844,255 (GRCm39) missense probably damaging 0.99
R4184:Tsc2 UTSW 17 24,850,990 (GRCm39) missense probably benign 0.43
R4435:Tsc2 UTSW 17 24,818,687 (GRCm39) missense probably benign 0.01
R4437:Tsc2 UTSW 17 24,818,687 (GRCm39) missense probably benign 0.01
R4474:Tsc2 UTSW 17 24,816,238 (GRCm39) missense probably damaging 0.98
R4703:Tsc2 UTSW 17 24,823,883 (GRCm39) missense probably benign 0.13
R4731:Tsc2 UTSW 17 24,822,249 (GRCm39) missense possibly damaging 0.72
R4732:Tsc2 UTSW 17 24,822,249 (GRCm39) missense possibly damaging 0.72
R4733:Tsc2 UTSW 17 24,822,249 (GRCm39) missense possibly damaging 0.72
R4817:Tsc2 UTSW 17 24,815,716 (GRCm39) splice site probably null
R4890:Tsc2 UTSW 17 24,819,009 (GRCm39) missense probably damaging 1.00
R4922:Tsc2 UTSW 17 24,819,343 (GRCm39) missense probably benign 0.22
R5119:Tsc2 UTSW 17 24,822,254 (GRCm39) missense probably benign 0.00
R5393:Tsc2 UTSW 17 24,819,370 (GRCm39) missense possibly damaging 0.89
R5785:Tsc2 UTSW 17 24,818,861 (GRCm39) splice site probably null
R5838:Tsc2 UTSW 17 24,832,190 (GRCm39) missense probably benign 0.01
R5857:Tsc2 UTSW 17 24,818,981 (GRCm39) missense probably damaging 0.99
R5911:Tsc2 UTSW 17 24,819,361 (GRCm39) missense possibly damaging 0.63
R5988:Tsc2 UTSW 17 24,839,740 (GRCm39) missense probably damaging 1.00
R6275:Tsc2 UTSW 17 24,819,394 (GRCm39) missense probably benign 0.00
R6290:Tsc2 UTSW 17 24,815,884 (GRCm39) missense probably benign 0.04
R6371:Tsc2 UTSW 17 24,845,688 (GRCm39) missense probably benign 0.00
R6467:Tsc2 UTSW 17 24,828,101 (GRCm39) missense probably benign 0.04
R6577:Tsc2 UTSW 17 24,829,473 (GRCm39) missense probably damaging 1.00
R6728:Tsc2 UTSW 17 24,840,098 (GRCm39) missense probably damaging 1.00
R6918:Tsc2 UTSW 17 24,832,203 (GRCm39) missense probably damaging 1.00
R6995:Tsc2 UTSW 17 24,847,028 (GRCm39) missense probably damaging 1.00
R7026:Tsc2 UTSW 17 24,845,713 (GRCm39) missense probably damaging 0.99
R7136:Tsc2 UTSW 17 24,832,254 (GRCm39) missense probably benign 0.00
R7236:Tsc2 UTSW 17 24,842,568 (GRCm39) missense possibly damaging 0.82
R7243:Tsc2 UTSW 17 24,818,604 (GRCm39) missense probably benign 0.02
R7249:Tsc2 UTSW 17 24,826,729 (GRCm39) missense probably damaging 1.00
R7450:Tsc2 UTSW 17 24,819,005 (GRCm39) missense probably damaging 1.00
R7529:Tsc2 UTSW 17 24,816,922 (GRCm39) missense probably damaging 0.98
R7637:Tsc2 UTSW 17 24,826,466 (GRCm39) missense probably benign 0.13
R7781:Tsc2 UTSW 17 24,827,089 (GRCm39) missense possibly damaging 0.52
R8005:Tsc2 UTSW 17 24,818,570 (GRCm39) missense probably damaging 0.98
R8262:Tsc2 UTSW 17 24,833,340 (GRCm39) missense probably benign 0.06
R8268:Tsc2 UTSW 17 24,818,984 (GRCm39) missense probably benign 0.44
R8400:Tsc2 UTSW 17 24,823,961 (GRCm39) missense possibly damaging 0.62
R9020:Tsc2 UTSW 17 24,845,691 (GRCm39) missense probably damaging 0.99
R9039:Tsc2 UTSW 17 24,826,489 (GRCm39) missense probably benign 0.01
R9065:Tsc2 UTSW 17 24,822,164 (GRCm39) missense probably benign 0.39
R9123:Tsc2 UTSW 17 24,823,802 (GRCm39) missense probably null 0.40
R9125:Tsc2 UTSW 17 24,823,802 (GRCm39) missense probably null 0.40
R9186:Tsc2 UTSW 17 24,823,862 (GRCm39) missense probably damaging 1.00
R9390:Tsc2 UTSW 17 24,823,824 (GRCm39) missense probably damaging 1.00
R9542:Tsc2 UTSW 17 24,819,308 (GRCm39) critical splice donor site probably null
R9721:Tsc2 UTSW 17 24,818,616 (GRCm39) nonsense probably null
Z1177:Tsc2 UTSW 17 24,839,753 (GRCm39) missense possibly damaging 0.61
Predicted Primers PCR Primer
(F):5'- ACAAAGCTAGCTTTCTGGGC -3'
(R):5'- CACTGGGGAAGTTCAGTACAG -3'

Sequencing Primer
(F):5'- TCCTGATCTACACTGAAGAGGCTG -3'
(R):5'- AGTTCAGTACAGCCAGAGATAC -3'
Posted On 2019-10-17