Incidental Mutation 'R4490:Tsc1'
| ID |
330664 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Tsc1
|
| Ensembl Gene |
ENSMUSG00000026812 |
| Gene Name |
TSC complex subunit 1 |
| Synonyms |
tuberous sclerosis 1, hamartin |
| MMRRC Submission |
041746-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R4490 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
2 |
| Chromosomal Location |
28531240-28581179 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 28560937 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Aspartic acid to Glycine
at position 265
(D265G)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000120888
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000028155]
[ENSMUST00000113867]
[ENSMUST00000113869]
[ENSMUST00000113870]
[ENSMUST00000133565]
[ENSMUST00000156857]
|
| AlphaFold |
Q9EP53 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000028155
AA Change: D265G
PolyPhen 2
Score 0.137 (Sensitivity: 0.92; Specificity: 0.86)
|
| SMART Domains |
Protein: ENSMUSP00000028155
Gene: ENSMUSG00000026812
AA Change: D265G
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Hamartin
|
2 |
715 |
2.2e-281 |
PFAM |
|
SCOP:d1eq1a_
|
723 |
886 |
4e-11 |
SMART |
|
low complexity region
|
974 |
990 |
N/A |
INTRINSIC |
|
low complexity region
|
1025 |
1042 |
N/A |
INTRINSIC |
|
low complexity region
|
1099 |
1117 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000113867
AA Change: D265G
PolyPhen 2
Score 0.137 (Sensitivity: 0.92; Specificity: 0.86)
|
| SMART Domains |
Protein: ENSMUSP00000109498
Gene: ENSMUSG00000026812
AA Change: D265G
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Hamartin
|
2 |
710 |
7.3e-279 |
PFAM |
|
SCOP:d1eq1a_
|
718 |
881 |
6e-11 |
SMART |
|
low complexity region
|
969 |
985 |
N/A |
INTRINSIC |
|
low complexity region
|
1020 |
1037 |
N/A |
INTRINSIC |
|
low complexity region
|
1094 |
1112 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000113869
AA Change: D265G
PolyPhen 2
Score 0.137 (Sensitivity: 0.92; Specificity: 0.86)
|
| SMART Domains |
Protein: ENSMUSP00000109500
Gene: ENSMUSG00000026812
AA Change: D265G
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Hamartin
|
7 |
716 |
6e-279 |
PFAM |
|
SCOP:d1eq1a_
|
724 |
887 |
4e-11 |
SMART |
|
low complexity region
|
975 |
991 |
N/A |
INTRINSIC |
|
low complexity region
|
1026 |
1043 |
N/A |
INTRINSIC |
|
low complexity region
|
1100 |
1118 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000113870
AA Change: D265G
PolyPhen 2
Score 0.137 (Sensitivity: 0.92; Specificity: 0.86)
|
| SMART Domains |
Protein: ENSMUSP00000109501
Gene: ENSMUSG00000026812
AA Change: D265G
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Hamartin
|
2 |
715 |
2.2e-281 |
PFAM |
|
SCOP:d1eq1a_
|
723 |
886 |
4e-11 |
SMART |
|
low complexity region
|
974 |
990 |
N/A |
INTRINSIC |
|
low complexity region
|
1025 |
1042 |
N/A |
INTRINSIC |
|
low complexity region
|
1099 |
1117 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000124507
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000125715
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000133565
AA Change: D265G
PolyPhen 2
Score 0.967 (Sensitivity: 0.77; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000120888
Gene: ENSMUSG00000026812
AA Change: D265G
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Hamartin
|
2 |
455 |
1.3e-198 |
PFAM |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000156857
AA Change: D265G
PolyPhen 2
Score 0.890 (Sensitivity: 0.82; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000115380
Gene: ENSMUSG00000026812
AA Change: D265G
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Hamartin
|
2 |
348 |
2.3e-170 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000153625
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000150274
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000139642
|
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.6%
- 10x: 97.2%
- 20x: 95.1%
|
| Validation Efficiency |
100% (45/45) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a growth inhibitory protein thought to play a role in the stabilization of tuberin. Mutations in this gene have been associated with tuberous sclerosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2009]
PHENOTYPE: Homozygous null mutants show liver hypoplasia, open neural tube and die by embryonic day 10.5-11.5. Heterozygotes develop kidney cystadenomas and liver hemangiomas. Conditional astrocyte-specific nulls show increased astrocyte numbers and seizures. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(38) : Targeted(7) Gene trapped(31)
|
| Other mutations in this stock |
Total: 40 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abl2 |
T |
C |
1: 156,461,349 (GRCm39) |
V417A |
probably damaging |
Het |
| Adgrb2 |
T |
C |
4: 129,906,121 (GRCm39) |
V881A |
possibly damaging |
Het |
| Arl5c |
G |
A |
11: 97,886,662 (GRCm39) |
R10* |
probably null |
Het |
| Atad1 |
A |
G |
19: 32,673,197 (GRCm39) |
C229R |
probably benign |
Het |
| Atp6v0a2 |
T |
C |
5: 124,784,674 (GRCm39) |
V319A |
probably damaging |
Het |
| Cage1 |
A |
G |
13: 38,207,393 (GRCm39) |
S257P |
possibly damaging |
Het |
| Ccndbp1 |
A |
G |
2: 120,842,876 (GRCm39) |
D179G |
probably damaging |
Het |
| Cngb3 |
T |
C |
4: 19,415,684 (GRCm39) |
I398T |
probably benign |
Het |
| Crmp1 |
A |
G |
5: 37,433,675 (GRCm39) |
D178G |
probably damaging |
Het |
| Csmd3 |
C |
T |
15: 48,177,429 (GRCm39) |
V370I |
possibly damaging |
Het |
| Dapk1 |
A |
G |
13: 60,865,942 (GRCm39) |
T180A |
probably benign |
Het |
| Dmtf1 |
A |
G |
5: 9,190,379 (GRCm39) |
|
probably benign |
Het |
| Dnah12 |
T |
C |
14: 26,455,758 (GRCm39) |
L827S |
possibly damaging |
Het |
| F5 |
T |
C |
1: 164,044,964 (GRCm39) |
V2084A |
probably benign |
Het |
| Fan1 |
A |
T |
7: 64,018,928 (GRCm39) |
S476T |
possibly damaging |
Het |
| Far2 |
T |
C |
6: 148,074,907 (GRCm39) |
L380P |
possibly damaging |
Het |
| Gbp2 |
A |
G |
3: 142,329,525 (GRCm39) |
N24S |
probably benign |
Het |
| Gm14325 |
T |
C |
2: 177,474,776 (GRCm39) |
H101R |
possibly damaging |
Het |
| Gpr55 |
C |
T |
1: 85,869,540 (GRCm39) |
V14M |
probably damaging |
Het |
| Herc6 |
A |
T |
6: 57,631,480 (GRCm39) |
Y724F |
probably damaging |
Het |
| Impg1 |
T |
A |
9: 80,301,341 (GRCm39) |
Q195L |
probably damaging |
Het |
| Inf2 |
T |
C |
12: 112,566,638 (GRCm39) |
F68L |
probably damaging |
Het |
| Kcnh8 |
T |
C |
17: 53,268,905 (GRCm39) |
|
probably null |
Het |
| Klb |
A |
G |
5: 65,533,137 (GRCm39) |
N482S |
probably benign |
Het |
| Kpnb1 |
A |
G |
11: 97,062,424 (GRCm39) |
V447A |
probably benign |
Het |
| Nckap5l |
G |
A |
15: 99,324,011 (GRCm39) |
P831S |
probably benign |
Het |
| Ncor2 |
A |
G |
5: 125,113,879 (GRCm39) |
|
probably null |
Het |
| Or4b1d |
A |
T |
2: 89,969,261 (GRCm39) |
V74D |
probably damaging |
Het |
| Pgm3 |
T |
C |
9: 86,443,893 (GRCm39) |
Y337C |
probably damaging |
Het |
| Prdm1 |
G |
T |
10: 44,322,903 (GRCm39) |
Y197* |
probably null |
Het |
| Prdm4 |
A |
T |
10: 85,736,763 (GRCm39) |
C626S |
probably damaging |
Het |
| Prex2 |
T |
A |
1: 11,232,487 (GRCm39) |
S851R |
probably benign |
Het |
| Ranbp6 |
A |
G |
19: 29,787,733 (GRCm39) |
L873P |
probably damaging |
Het |
| Rin2 |
A |
G |
2: 145,664,194 (GRCm39) |
T23A |
possibly damaging |
Het |
| Rxra |
G |
T |
2: 27,631,207 (GRCm39) |
R118L |
probably damaging |
Het |
| Spice1 |
T |
C |
16: 44,202,476 (GRCm39) |
L750P |
probably damaging |
Het |
| Trpm1 |
C |
T |
7: 63,858,660 (GRCm39) |
Q228* |
probably null |
Het |
| Usp29 |
T |
C |
7: 6,964,949 (GRCm39) |
I264T |
possibly damaging |
Het |
| Vmn2r26 |
T |
C |
6: 124,027,697 (GRCm39) |
L479P |
possibly damaging |
Het |
| Zfp9 |
A |
G |
6: 118,442,273 (GRCm39) |
S130P |
probably benign |
Het |
|
| Other mutations in Tsc1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00333:Tsc1
|
APN |
2 |
28,551,623 (GRCm39) |
missense |
probably damaging |
0.98 |
|
IGL00770:Tsc1
|
APN |
2 |
28,555,023 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL00774:Tsc1
|
APN |
2 |
28,555,023 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL00835:Tsc1
|
APN |
2 |
28,562,478 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
IGL00971:Tsc1
|
APN |
2 |
28,560,952 (GRCm39) |
nonsense |
probably null |
|
|
IGL01808:Tsc1
|
APN |
2 |
28,552,519 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02281:Tsc1
|
APN |
2 |
28,553,607 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03068:Tsc1
|
APN |
2 |
28,571,270 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Cassava
|
UTSW |
2 |
28,561,898 (GRCm39) |
splice site |
probably null |
|
|
R0077:Tsc1
|
UTSW |
2 |
28,568,955 (GRCm39) |
splice site |
probably benign |
|
|
R0149:Tsc1
|
UTSW |
2 |
28,560,913 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0605:Tsc1
|
UTSW |
2 |
28,561,790 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0737:Tsc1
|
UTSW |
2 |
28,560,942 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R1199:Tsc1
|
UTSW |
2 |
28,555,638 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1751:Tsc1
|
UTSW |
2 |
28,566,038 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R1757:Tsc1
|
UTSW |
2 |
28,576,125 (GRCm39) |
missense |
probably benign |
0.05 |
|
R1807:Tsc1
|
UTSW |
2 |
28,576,125 (GRCm39) |
missense |
probably benign |
0.05 |
|
R2014:Tsc1
|
UTSW |
2 |
28,555,649 (GRCm39) |
splice site |
probably benign |
|
|
R2284:Tsc1
|
UTSW |
2 |
28,555,109 (GRCm39) |
missense |
possibly damaging |
0.85 |
|
R3786:Tsc1
|
UTSW |
2 |
28,577,154 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4707:Tsc1
|
UTSW |
2 |
28,562,419 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4751:Tsc1
|
UTSW |
2 |
28,569,093 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R4794:Tsc1
|
UTSW |
2 |
28,551,702 (GRCm39) |
splice site |
probably null |
|
|
R4906:Tsc1
|
UTSW |
2 |
28,565,201 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R5020:Tsc1
|
UTSW |
2 |
28,566,531 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5401:Tsc1
|
UTSW |
2 |
28,576,920 (GRCm39) |
nonsense |
probably null |
|
|
R5708:Tsc1
|
UTSW |
2 |
28,555,197 (GRCm39) |
intron |
probably benign |
|
|
R6435:Tsc1
|
UTSW |
2 |
28,566,464 (GRCm39) |
missense |
probably benign |
0.08 |
|
R6469:Tsc1
|
UTSW |
2 |
28,561,898 (GRCm39) |
splice site |
probably null |
|
|
R6502:Tsc1
|
UTSW |
2 |
28,555,613 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6617:Tsc1
|
UTSW |
2 |
28,577,001 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R7098:Tsc1
|
UTSW |
2 |
28,565,744 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7503:Tsc1
|
UTSW |
2 |
28,577,088 (GRCm39) |
missense |
possibly damaging |
0.50 |
|
R7608:Tsc1
|
UTSW |
2 |
28,548,748 (GRCm39) |
missense |
probably benign |
0.01 |
|
R7677:Tsc1
|
UTSW |
2 |
28,562,829 (GRCm39) |
missense |
probably benign |
0.11 |
|
R7791:Tsc1
|
UTSW |
2 |
28,571,960 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8021:Tsc1
|
UTSW |
2 |
28,576,901 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R8203:Tsc1
|
UTSW |
2 |
28,563,007 (GRCm39) |
splice site |
probably null |
|
|
R8228:Tsc1
|
UTSW |
2 |
28,566,141 (GRCm39) |
missense |
probably benign |
0.23 |
|
R9057:Tsc1
|
UTSW |
2 |
28,575,874 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9088:Tsc1
|
UTSW |
2 |
28,552,617 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R9201:Tsc1
|
UTSW |
2 |
28,576,791 (GRCm39) |
missense |
probably benign |
|
|
R9386:Tsc1
|
UTSW |
2 |
28,561,858 (GRCm39) |
missense |
probably benign |
|
|
R9731:Tsc1
|
UTSW |
2 |
28,566,486 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9780:Tsc1
|
UTSW |
2 |
28,565,761 (GRCm39) |
missense |
probably damaging |
0.98 |
|
| Predicted Primers |
PCR Primer
(F):5'- AAGTGGCTTGTTAACTGATGGC -3'
(R):5'- GCGATTCAGAAGTCCCTAGGTAG -3'
Sequencing Primer
(F):5'- CTGATGGCTAATTTTTATCCTAGTGC -3'
(R):5'- CCCTAGGTAGTAAATGATGAAGTTGC -3'
|
| Posted On |
2015-07-21 |
Incidental Mutation