Incidental Mutation 'R4435:Tsc2'
| ID |
329504 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Tsc2
|
| Ensembl Gene |
ENSMUSG00000002496 |
| Gene Name |
tuberous sclerosis 2 |
| Synonyms |
tuberin, Nafld |
| MMRRC Submission |
041149-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R4435 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
17 |
| Chromosomal Location |
24595816-24632630 bp(-) (GRCm38) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to A
at 24599713 bp (GRCm38)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Proline to Leucine
at position 1450
(P1450L)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000154338
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000035565]
[ENSMUST00000097373]
[ENSMUST00000226284]
[ENSMUST00000226398]
[ENSMUST00000228412]
[ENSMUST00000227745]
[ENSMUST00000227607]
[ENSMUST00000227804]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000035565
|
| SMART Domains |
Protein: ENSMUSP00000049296
Gene: ENSMUSG00000032855
| Domain | Start | End | E-Value | Type |
|---|
|
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 benign
Transcript: ENSMUST00000097373
AA Change: P1384L
PolyPhen 2
Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
|
| SMART Domains |
Protein: ENSMUSP00000094986
Gene: ENSMUSG00000002496
AA Change: P1384L
| Domain | Start | End | E-Value | Type |
|---|
|
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 benign
Transcript: ENSMUST00000226284
AA Change: P1427L
PolyPhen 2
Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000226398
AA Change: P1384L
PolyPhen 2
Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000226428
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000226473
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000226691
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000227094
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000227107
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000227330
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000227432
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000228412
AA Change: P1383L
PolyPhen 2
Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000227745
AA Change: P1450L
PolyPhen 2
Score 0.011 (Sensitivity: 0.96; Specificity: 0.78)
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000227607
AA Change: P1325L
PolyPhen 2
Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000227804
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000227658
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000228729
|
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.6%
- 10x: 97.3%
- 20x: 95.4%
|
| Validation Efficiency |
|
| 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: 39 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adam6b |
A |
C |
12: 113,490,661 |
Q366P |
probably damaging |
Het |
| Adamts16 |
G |
A |
13: 70,779,518 |
|
probably benign |
Het |
| Ank3 |
C |
T |
10: 69,987,070 |
S523L |
probably damaging |
Het |
| Arap1 |
C |
A |
7: 101,390,254 |
R574S |
possibly damaging |
Het |
| Arhgap25 |
T |
C |
6: 87,462,938 |
I576V |
possibly damaging |
Het |
| Ascc3 |
T |
A |
10: 50,721,885 |
V1283D |
probably benign |
Het |
| Asnsd1 |
A |
T |
1: 53,348,073 |
|
probably null |
Het |
| Asrgl1 |
C |
T |
19: 9,119,199 |
V125I |
probably damaging |
Het |
| Bccip |
A |
G |
7: 133,719,213 |
R239G |
probably benign |
Het |
| Cdyl |
T |
C |
13: 35,858,250 |
|
probably null |
Het |
| Cyfip1 |
T |
C |
7: 55,900,041 |
I650T |
probably damaging |
Het |
| Dennd4c |
C |
A |
4: 86,798,075 |
Q506K |
probably benign |
Het |
| Fam135b |
T |
C |
15: 71,448,739 |
D1313G |
probably damaging |
Het |
| Fam169a |
A |
G |
13: 97,126,740 |
D567G |
probably damaging |
Het |
| Gm5134 |
T |
G |
10: 75,995,824 |
S366A |
probably damaging |
Het |
| Gm5849 |
T |
A |
3: 90,777,875 |
K1M |
probably null |
Het |
| Gpn3 |
A |
G |
5: 122,382,052 |
D223G |
probably benign |
Het |
| Hk1 |
A |
G |
10: 62,275,844 |
Y713H |
probably damaging |
Het |
| Ifih1 |
A |
G |
2: 62,645,890 |
L14P |
probably damaging |
Het |
| Kmt2c |
A |
T |
5: 25,314,877 |
N2078K |
possibly damaging |
Het |
| Maf |
T |
A |
8: 115,706,853 |
E4V |
unknown |
Het |
| Mbtd1 |
T |
A |
11: 93,932,222 |
D489E |
probably benign |
Het |
| Myrip |
C |
T |
9: 120,335,614 |
|
probably benign |
Het |
| Nedd4l |
A |
G |
18: 65,212,825 |
D816G |
possibly damaging |
Het |
| Nwd1 |
T |
C |
8: 72,688,136 |
V934A |
possibly damaging |
Het |
| Olfr290 |
A |
G |
7: 84,916,021 |
M81V |
probably benign |
Het |
| Olfr446 |
T |
A |
6: 42,928,089 |
I286N |
probably damaging |
Het |
| Psd |
A |
T |
19: 46,314,494 |
I158N |
probably damaging |
Het |
| Ptprq |
A |
G |
10: 107,685,055 |
V752A |
possibly damaging |
Het |
| Robo4 |
CGG |
CG |
9: 37,411,490 |
|
probably null |
Het |
| Senp2 |
T |
A |
16: 22,014,241 |
V93E |
possibly damaging |
Het |
| Siah1b |
G |
A |
X: 164,071,692 |
P131S |
probably damaging |
Het |
| Slc38a4 |
T |
C |
15: 97,009,018 |
S280G |
probably benign |
Het |
| Sos2 |
T |
C |
12: 69,614,699 |
E666G |
possibly damaging |
Het |
| Strip2 |
T |
C |
6: 29,925,050 |
V129A |
probably benign |
Het |
| Ttn |
T |
C |
2: 76,916,875 |
E4610G |
probably benign |
Het |
| Uimc1 |
T |
C |
13: 55,075,823 |
E212G |
probably damaging |
Het |
| Zc3h18 |
T |
C |
8: 122,413,952 |
|
probably null |
Het |
| Zswim3 |
T |
A |
2: 164,820,643 |
C348S |
probably benign |
Het |
|
| Other mutations in Tsc2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00231:Tsc2
|
APN |
17 |
24608107 |
missense |
probably damaging |
1.00 |
|
IGL00985:Tsc2
|
APN |
17 |
24597131 |
missense |
probably damaging |
1.00 |
|
IGL01386:Tsc2
|
APN |
17 |
24613285 |
missense |
probably damaging |
1.00 |
|
IGL01468:Tsc2
|
APN |
17 |
24621097 |
missense |
possibly damaging |
0.90 |
|
IGL01530:Tsc2
|
APN |
17 |
24622662 |
missense |
possibly damaging |
0.76 |
|
IGL02390:Tsc2
|
APN |
17 |
24600453 |
missense |
probably damaging |
1.00 |
|
IGL02398:Tsc2
|
APN |
17 |
24621729 |
missense |
probably damaging |
1.00 |
|
IGL02741:Tsc2
|
APN |
17 |
24629969 |
missense |
probably damaging |
1.00 |
|
IGL03191:Tsc2
|
APN |
17 |
24628054 |
missense |
probably damaging |
1.00 |
|
IGL03372:Tsc2
|
APN |
17 |
24619470 |
missense |
probably damaging |
1.00 |
|
IGL03412:Tsc2
|
APN |
17 |
24597068 |
missense |
probably damaging |
0.98 |
|
Twitch
|
UTSW |
17 |
24596742 |
splice site |
probably null |
|
|
PIT4515001:Tsc2
|
UTSW |
17 |
24621147 |
missense |
probably benign |
0.15 |
|
R0025:Tsc2
|
UTSW |
17 |
24631004 |
splice site |
probably benign |
|
|
R0025:Tsc2
|
UTSW |
17 |
24631004 |
splice site |
probably benign |
|
|
R0138:Tsc2
|
UTSW |
17 |
24599626 |
missense |
possibly damaging |
0.65 |
|
R0540:Tsc2
|
UTSW |
17 |
24621712 |
missense |
probably damaging |
1.00 |
|
R0570:Tsc2
|
UTSW |
17 |
24626727 |
missense |
probably damaging |
1.00 |
|
R0607:Tsc2
|
UTSW |
17 |
24621712 |
missense |
probably damaging |
1.00 |
|
R0826:Tsc2
|
UTSW |
17 |
24596958 |
missense |
probably benign |
0.04 |
|
R1430:Tsc2
|
UTSW |
17 |
24599023 |
critical splice donor site |
probably null |
|
|
R1440:Tsc2
|
UTSW |
17 |
24614392 |
missense |
probably damaging |
1.00 |
|
R1466:Tsc2
|
UTSW |
17 |
24608973 |
missense |
probably damaging |
1.00 |
|
R1466:Tsc2
|
UTSW |
17 |
24608973 |
missense |
probably damaging |
1.00 |
|
R1541:Tsc2
|
UTSW |
17 |
24631976 |
missense |
probably damaging |
1.00 |
|
R1717:Tsc2
|
UTSW |
17 |
24597068 |
missense |
probably damaging |
0.98 |
|
R1799:Tsc2
|
UTSW |
17 |
24604408 |
missense |
probably benign |
|
|
R2030:Tsc2
|
UTSW |
17 |
24623470 |
splice site |
probably benign |
|
|
R2147:Tsc2
|
UTSW |
17 |
24621142 |
missense |
possibly damaging |
0.62 |
|
R2888:Tsc2
|
UTSW |
17 |
24631995 |
critical splice donor site |
probably null |
|
|
R3609:Tsc2
|
UTSW |
17 |
24622550 |
missense |
possibly damaging |
0.74 |
|
R3610:Tsc2
|
UTSW |
17 |
24622550 |
missense |
possibly damaging |
0.74 |
|
R3811:Tsc2
|
UTSW |
17 |
24629037 |
missense |
probably benign |
0.09 |
|
R3895:Tsc2
|
UTSW |
17 |
24599812 |
missense |
probably damaging |
1.00 |
|
R3962:Tsc2
|
UTSW |
17 |
24621166 |
splice site |
probably benign |
|
|
R3971:Tsc2
|
UTSW |
17 |
24623588 |
missense |
probably damaging |
1.00 |
|
R4018:Tsc2
|
UTSW |
17 |
24625281 |
missense |
probably damaging |
0.99 |
|
R4184:Tsc2
|
UTSW |
17 |
24632016 |
missense |
probably benign |
0.43 |
|
R4437:Tsc2
|
UTSW |
17 |
24599713 |
missense |
probably benign |
0.01 |
|
R4474:Tsc2
|
UTSW |
17 |
24597264 |
missense |
probably damaging |
0.98 |
|
R4703:Tsc2
|
UTSW |
17 |
24604909 |
missense |
probably benign |
0.13 |
|
R4731:Tsc2
|
UTSW |
17 |
24603275 |
missense |
possibly damaging |
0.72 |
|
R4732:Tsc2
|
UTSW |
17 |
24603275 |
missense |
possibly damaging |
0.72 |
|
R4733:Tsc2
|
UTSW |
17 |
24603275 |
missense |
possibly damaging |
0.72 |
|
R4817:Tsc2
|
UTSW |
17 |
24596742 |
splice site |
probably null |
|
|
R4890:Tsc2
|
UTSW |
17 |
24600035 |
missense |
probably damaging |
1.00 |
|
R4922:Tsc2
|
UTSW |
17 |
24600369 |
missense |
probably benign |
0.22 |
|
R5119:Tsc2
|
UTSW |
17 |
24603280 |
missense |
probably benign |
0.00 |
|
R5393:Tsc2
|
UTSW |
17 |
24600396 |
missense |
possibly damaging |
0.89 |
|
R5785:Tsc2
|
UTSW |
17 |
24599887 |
splice site |
probably null |
|
|
R5838:Tsc2
|
UTSW |
17 |
24613216 |
missense |
probably benign |
0.01 |
|
R5857:Tsc2
|
UTSW |
17 |
24600007 |
missense |
probably damaging |
0.99 |
|
R5911:Tsc2
|
UTSW |
17 |
24600387 |
missense |
possibly damaging |
0.63 |
|
R5988:Tsc2
|
UTSW |
17 |
24620766 |
missense |
probably damaging |
1.00 |
|
R6275:Tsc2
|
UTSW |
17 |
24600420 |
missense |
probably benign |
0.00 |
|
R6290:Tsc2
|
UTSW |
17 |
24596910 |
missense |
probably benign |
0.04 |
|
R6371:Tsc2
|
UTSW |
17 |
24626714 |
missense |
probably benign |
0.00 |
|
R6467:Tsc2
|
UTSW |
17 |
24609127 |
missense |
probably benign |
0.04 |
|
R6577:Tsc2
|
UTSW |
17 |
24610499 |
missense |
probably damaging |
1.00 |
|
R6728:Tsc2
|
UTSW |
17 |
24621124 |
missense |
probably damaging |
1.00 |
|
R6918:Tsc2
|
UTSW |
17 |
24613229 |
missense |
probably damaging |
1.00 |
|
R6995:Tsc2
|
UTSW |
17 |
24628054 |
missense |
probably damaging |
1.00 |
|
R7026:Tsc2
|
UTSW |
17 |
24626739 |
missense |
probably damaging |
0.99 |
|
R7136:Tsc2
|
UTSW |
17 |
24613280 |
missense |
probably benign |
0.00 |
|
R7236:Tsc2
|
UTSW |
17 |
24623594 |
missense |
possibly damaging |
0.82 |
|
R7243:Tsc2
|
UTSW |
17 |
24599630 |
missense |
probably benign |
0.02 |
|
R7249:Tsc2
|
UTSW |
17 |
24607755 |
missense |
probably damaging |
1.00 |
|
R7450:Tsc2
|
UTSW |
17 |
24600031 |
missense |
probably damaging |
1.00 |
|
R7522:Tsc2
|
UTSW |
17 |
24630965 |
missense |
probably damaging |
1.00 |
|
R7529:Tsc2
|
UTSW |
17 |
24597948 |
missense |
probably damaging |
0.98 |
|
R7637:Tsc2
|
UTSW |
17 |
24607492 |
missense |
probably benign |
0.13 |
|
R7781:Tsc2
|
UTSW |
17 |
24608115 |
missense |
possibly damaging |
0.52 |
|
R8005:Tsc2
|
UTSW |
17 |
24599596 |
missense |
probably damaging |
0.98 |
|
R8262:Tsc2
|
UTSW |
17 |
24614366 |
missense |
probably benign |
0.06 |
|
R8268:Tsc2
|
UTSW |
17 |
24600010 |
missense |
probably benign |
0.44 |
|
R8400:Tsc2
|
UTSW |
17 |
24604987 |
missense |
possibly damaging |
0.62 |
|
R9020:Tsc2
|
UTSW |
17 |
24626717 |
missense |
probably damaging |
0.99 |
|
R9039:Tsc2
|
UTSW |
17 |
24607515 |
missense |
probably benign |
0.01 |
|
R9065:Tsc2
|
UTSW |
17 |
24603190 |
missense |
probably benign |
0.39 |
|
R9123:Tsc2
|
UTSW |
17 |
24604828 |
missense |
probably null |
0.40 |
|
R9125:Tsc2
|
UTSW |
17 |
24604828 |
missense |
probably null |
0.40 |
|
R9186:Tsc2
|
UTSW |
17 |
24604888 |
missense |
probably damaging |
1.00 |
|
R9390:Tsc2
|
UTSW |
17 |
24604850 |
missense |
probably damaging |
1.00 |
|
R9542:Tsc2
|
UTSW |
17 |
24600334 |
critical splice donor site |
probably null |
|
|
R9721:Tsc2
|
UTSW |
17 |
24599642 |
nonsense |
probably null |
|
|
Z1177:Tsc2
|
UTSW |
17 |
24620779 |
missense |
possibly damaging |
0.61 |
|
| Predicted Primers |
PCR Primer
(F):5'- TATCCCCTGGAGTTGGTAGC -3'
(R):5'- GCCTTTGAGCAAGTCTAGCTC -3'
Sequencing Primer
(F):5'- AGCAACCTGGGATTTGTGCC -3'
(R):5'- GAGCAAGTCTAGCTCTTCTCCGG -3'
|
| Posted On |
2015-07-21 |
Incidental Mutation