Incidental Mutation 'R5857:Tsc2'
ID 454980
Institutional Source Beutler Lab
Gene Symbol Tsc2
Ensembl Gene ENSMUSG00000002496
Gene Name TSC complex subunit 2
Synonyms tuberin, Nafld, tuberous sclerosis 2
MMRRC Submission 044069-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R5857 (G1)
Quality Score 188
Status Validated
Chromosome 17
Chromosomal Location 24814790-24851604 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 24818981 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glutamic Acid to Glycine at position 1352 (E1352G)
Ref Sequence ENSEMBL: ENSMUSP00000154338 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000035565] [ENSMUST00000097373] [ENSMUST00000226284] [ENSMUST00000226398] [ENSMUST00000227607] [ENSMUST00000227745] [ENSMUST00000228412] [ENSMUST00000227804]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000035565
SMART Domains Protein: ENSMUSP00000049296
Gene: ENSMUSG00000032855

DomainStartEndE-ValueType
signal peptide 1 23 N/A INTRINSIC
LRRNT 32 71 1.61e-8 SMART
LRR_TYP 90 113 2.47e-5 SMART
LRRCT 125 177 3.84e-12 SMART
WSC 177 271 6.93e-34 SMART
PKD 272 355 2.72e-15 SMART
CLECT 406 530 5.72e-20 SMART
low complexity region 545 558 N/A INTRINSIC
low complexity region 763 788 N/A INTRINSIC
PKD 930 1008 1.06e-8 SMART
PKD 1015 1119 2.26e-12 SMART
PKD 1122 1205 2.03e-14 SMART
PKD 1208 1288 1.14e-17 SMART
PKD 1290 1373 2.35e-10 SMART
PKD 1374 1459 7.63e-10 SMART
PKD 1464 1541 1.95e-16 SMART
PKD 1544 1625 1.05e-16 SMART
PKD 1631 1714 1.93e-1 SMART
PKD 1716 1798 2.21e-15 SMART
PKD 1799 1882 5.7e-9 SMART
PKD 1884 1964 1.56e-6 SMART
PKD 1968 2056 3.1e-10 SMART
PKD 2057 2140 1.74e-13 SMART
Pfam:REJ 2167 2610 1e-108 PFAM
low complexity region 2697 2706 N/A INTRINSIC
GPS 3003 3052 1.33e-12 SMART
transmembrane domain 3065 3087 N/A INTRINSIC
LH2 3110 3224 3.5e-18 SMART
transmembrane domain 3275 3294 N/A INTRINSIC
transmembrane domain 3314 3336 N/A INTRINSIC
low complexity region 3357 3378 N/A INTRINSIC
low complexity region 3479 3492 N/A INTRINSIC
transmembrane domain 3547 3569 N/A INTRINSIC
low complexity region 3573 3591 N/A INTRINSIC
low complexity region 3626 3639 N/A INTRINSIC
low complexity region 3661 3676 N/A INTRINSIC
Pfam:PKD_channel 3701 4103 7.1e-125 PFAM
low complexity region 4153 4172 N/A INTRINSIC
low complexity region 4238 4256 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000097373
AA Change: E1286G

PolyPhen 2 Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000094986
Gene: ENSMUSG00000002496
AA Change: E1286G

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 noncoding transcript
Transcript: ENSMUST00000116692
Predicted Effect probably damaging
Transcript: ENSMUST00000226284
AA Change: E1329G

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)
Predicted Effect probably damaging
Transcript: ENSMUST00000226398
AA Change: E1286G

PolyPhen 2 Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000226428
Predicted Effect probably damaging
Transcript: ENSMUST00000227607
AA Change: E1227G

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)
Predicted Effect probably damaging
Transcript: ENSMUST00000227745
AA Change: E1352G

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
Predicted Effect possibly damaging
Transcript: ENSMUST00000228412
AA Change: E1285G

PolyPhen 2 Score 0.933 (Sensitivity: 0.80; Specificity: 0.94)
Predicted Effect probably benign
Transcript: ENSMUST00000227804
Predicted Effect noncoding transcript
Transcript: ENSMUST00000227330
Predicted Effect noncoding transcript
Transcript: ENSMUST00000227432
Predicted Effect probably benign
Transcript: ENSMUST00000227658
Predicted Effect probably benign
Transcript: ENSMUST00000227107
Predicted Effect noncoding transcript
Transcript: ENSMUST00000226691
Predicted Effect noncoding transcript
Transcript: ENSMUST00000227094
Predicted Effect noncoding transcript
Transcript: ENSMUST00000226985
Predicted Effect noncoding transcript
Transcript: ENSMUST00000226473
Predicted Effect noncoding transcript
Transcript: ENSMUST00000228729
Meta Mutation Damage Score 0.2933 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.6%
  • 10x: 97.9%
  • 20x: 93.6%
Validation Efficiency 95% (55/58)
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: 50 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700030K09Rik A G 8: 73,203,369 (GRCm39) I266V probably benign Het
Anks6 C T 4: 47,039,736 (GRCm39) A492T possibly damaging Het
Ano1 A T 7: 144,190,840 (GRCm39) C415S probably benign Het
Anxa3 T A 5: 96,976,651 (GRCm39) probably null Het
Apob T C 12: 8,065,397 (GRCm39) V4089A probably benign Het
Arhgap23 C T 11: 97,342,405 (GRCm39) A229V possibly damaging Het
Atad5 T C 11: 80,022,155 (GRCm39) F1447L probably benign Het
Btbd8 T A 5: 107,609,398 (GRCm39) D212E probably damaging Het
Ccdc38 G T 10: 93,398,695 (GRCm39) A58S possibly damaging Het
Cep112 T C 11: 108,422,297 (GRCm39) probably benign Het
Col4a2 G A 8: 11,475,442 (GRCm39) G622D probably damaging Het
Crhbp T A 13: 95,578,740 (GRCm39) Q134L probably benign Het
Ctnnbl1 T C 2: 157,631,018 (GRCm39) S145P probably damaging Het
Cyp4f16 T A 17: 32,755,998 (GRCm39) L9Q probably damaging Het
Dchs2 T G 3: 83,177,620 (GRCm39) I891S possibly damaging Het
Disp3 A T 4: 148,333,640 (GRCm39) V1066D probably benign Het
Dlgap1 A G 17: 71,122,388 (GRCm39) probably benign Het
Dnah3 TTCCTC TTC 7: 119,550,244 (GRCm39) probably benign Het
Efl1 T A 7: 82,412,397 (GRCm39) C929S probably benign Het
Gatb T C 3: 85,483,239 (GRCm39) F82S probably damaging Het
Gk5 C A 9: 96,001,508 (GRCm39) S2* probably null Het
Gpr135 G A 12: 72,117,614 (GRCm39) A51V probably benign Het
Hoxa9 T A 6: 52,201,277 (GRCm39) N255Y probably damaging Het
Igkv8-18 T C 6: 70,332,904 (GRCm39) V15A probably benign Het
Ism2 T C 12: 87,326,835 (GRCm39) D368G probably damaging Het
Krtap6-2 A T 16: 89,216,530 (GRCm39) S146T unknown Het
Lama1 T A 17: 68,114,838 (GRCm39) L2329H probably damaging Het
Llgl2 T A 11: 115,741,107 (GRCm39) I507N probably damaging Het
Lmna GCTGCCCACAC GC 3: 88,389,838 (GRCm39) probably benign Het
Lrfn3 A T 7: 30,058,863 (GRCm39) I454N possibly damaging Het
Mdn1 C A 4: 32,670,646 (GRCm39) T437K probably benign Het
Nat8f3 T C 6: 85,738,735 (GRCm39) Y9C probably damaging Het
Niban2 T A 2: 32,799,920 (GRCm39) N82K probably benign Het
Nlrp4d C A 7: 10,116,304 (GRCm39) G156V noncoding transcript Het
Npnt A T 3: 132,614,110 (GRCm39) C167S probably damaging Het
Nr3c2 A G 8: 77,635,496 (GRCm39) N199S possibly damaging Het
Or10x4 T G 1: 174,218,674 (GRCm39) I13R possibly damaging Het
Or8b12i C T 9: 20,082,535 (GRCm39) D111N probably damaging Het
Or8b37 T G 9: 37,959,049 (GRCm39) V177G probably benign Het
Pabpc1l T A 2: 163,886,175 (GRCm39) probably null Het
Pi4ka A G 16: 17,176,848 (GRCm39) I366T probably benign Het
Prl7a1 A T 13: 27,824,684 (GRCm39) D50E probably damaging Het
Rad52 T G 6: 119,887,968 (GRCm39) probably null Het
Rbm19 T A 5: 120,271,007 (GRCm39) L610Q probably damaging Het
Rnd2 C T 11: 101,359,825 (GRCm39) L57F probably damaging Het
Scube1 G T 15: 83,491,461 (GRCm39) probably benign Het
Sptbn4 G T 7: 27,118,138 (GRCm39) R314S possibly damaging Het
Togaram1 T A 12: 65,042,331 (GRCm39) I1130K possibly damaging Het
Ube2d2a A G 18: 35,938,596 (GRCm39) T142A probably benign Het
Vps18 T C 2: 119,128,014 (GRCm39) Y946H probably damaging 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
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
R7522:Tsc2 UTSW 17 24,849,939 (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'- AGCCGTCCAATATCAATCTTGTC -3'
(R):5'- TGTGAGCTGGATAGGCCTTC -3'

Sequencing Primer
(F):5'- TGTCCCCTAGGTCTCCAAGGATG -3'
(R):5'- CCCTCTATCTGGGTGGCATTTATTG -3'
Posted On 2017-02-10