Incidental Mutation 'R2284:Tsc1'
| ID |
243234 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Tsc1
|
| Ensembl Gene |
ENSMUSG00000026812 |
| Gene Name |
TSC complex subunit 1 |
| Synonyms |
tuberous sclerosis 1, hamartin |
| MMRRC Submission |
040283-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R2284 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
2 |
| Chromosomal Location |
28531240-28581179 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to A
at 28555109 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Valine to Isoleucine
at position 200
(V200I)
|
| 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: V200I
PolyPhen 2
Score 0.436 (Sensitivity: 0.89; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000028155
Gene: ENSMUSG00000026812
AA Change: V200I
| 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: V200I
PolyPhen 2
Score 0.436 (Sensitivity: 0.89; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000109498
Gene: ENSMUSG00000026812
AA Change: V200I
| 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: V200I
PolyPhen 2
Score 0.436 (Sensitivity: 0.89; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000109500
Gene: ENSMUSG00000026812
AA Change: V200I
| 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: V200I
PolyPhen 2
Score 0.436 (Sensitivity: 0.89; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000109501
Gene: ENSMUSG00000026812
AA Change: V200I
| 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 |
possibly damaging
Transcript: ENSMUST00000133565
AA Change: V200I
PolyPhen 2
Score 0.848 (Sensitivity: 0.83; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000120888
Gene: ENSMUSG00000026812
AA Change: V200I
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Hamartin
|
2 |
455 |
1.3e-198 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000150274
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000156857
AA Change: V200I
PolyPhen 2
Score 0.447 (Sensitivity: 0.89; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000115380
Gene: ENSMUSG00000026812
AA Change: V200I
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Hamartin
|
2 |
348 |
2.3e-170 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000153625
|
| Meta Mutation Damage Score |
0.1299 |
| Coding Region Coverage |
- 1x: 99.1%
- 3x: 98.6%
- 10x: 97.3%
- 20x: 95.0%
|
| Validation Efficiency |
100% (32/32) |
| 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: 32 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adipoq |
C |
T |
16: 22,976,237 (GRCm39) |
Q213* |
probably null |
Het |
| Adsl |
C |
T |
15: 80,848,096 (GRCm39) |
P278L |
probably damaging |
Het |
| Bcas2 |
T |
C |
3: 103,085,678 (GRCm39) |
S187P |
probably damaging |
Het |
| Ccdc88a |
T |
C |
11: 29,444,099 (GRCm39) |
|
probably null |
Het |
| Cryzl1 |
C |
T |
16: 91,491,193 (GRCm39) |
|
probably benign |
Het |
| Csl |
T |
A |
10: 99,594,321 (GRCm39) |
D248V |
possibly damaging |
Het |
| Dip2a |
A |
C |
10: 76,149,027 (GRCm39) |
V247G |
probably benign |
Het |
| Fat2 |
T |
C |
11: 55,173,186 (GRCm39) |
D2509G |
probably damaging |
Het |
| Gldn |
G |
A |
9: 54,193,849 (GRCm39) |
W14* |
probably null |
Het |
| Gm5698 |
C |
T |
1: 31,016,964 (GRCm39) |
R29Q |
possibly damaging |
Het |
| Gm5830 |
A |
T |
1: 78,945,415 (GRCm39) |
|
noncoding transcript |
Het |
| Gtf2ird2 |
A |
G |
5: 134,246,025 (GRCm39) |
D761G |
probably benign |
Het |
| Hdac10 |
T |
C |
15: 89,011,607 (GRCm39) |
Q159R |
probably benign |
Het |
| Hhatl |
T |
C |
9: 121,618,648 (GRCm39) |
Y118C |
probably damaging |
Het |
| Iho1 |
C |
T |
9: 108,298,672 (GRCm39) |
E49K |
probably damaging |
Het |
| Klrd1 |
A |
G |
6: 129,575,344 (GRCm39) |
H127R |
probably benign |
Het |
| Krtap31-1 |
C |
T |
11: 99,799,081 (GRCm39) |
Q95* |
probably null |
Het |
| Map2 |
C |
T |
1: 66,453,227 (GRCm39) |
P548S |
probably damaging |
Het |
| Mki67 |
A |
G |
7: 135,301,674 (GRCm39) |
V1120A |
probably damaging |
Het |
| Mslnl |
G |
A |
17: 25,961,908 (GRCm39) |
V128M |
probably damaging |
Het |
| Mtmr12 |
T |
A |
15: 12,245,097 (GRCm39) |
M204K |
probably damaging |
Het |
| Muc6 |
T |
C |
7: 141,217,837 (GRCm39) |
T2279A |
possibly damaging |
Het |
| Naip6 |
C |
T |
13: 100,437,108 (GRCm39) |
A472T |
probably benign |
Het |
| Nlrp1b |
A |
G |
11: 71,047,110 (GRCm39) |
S1084P |
probably benign |
Het |
| Nr2f1 |
C |
A |
13: 78,343,581 (GRCm39) |
V81F |
probably damaging |
Het |
| Nrxn3 |
T |
A |
12: 89,477,135 (GRCm39) |
N803K |
probably damaging |
Het |
| Or5l14 |
A |
G |
2: 87,793,137 (GRCm39) |
L33P |
probably damaging |
Het |
| Ptpre |
A |
G |
7: 135,271,510 (GRCm39) |
H375R |
probably benign |
Het |
| Vmn1r42 |
A |
G |
6: 89,821,681 (GRCm39) |
I296T |
probably benign |
Het |
| Vmn1r67 |
A |
T |
7: 10,181,600 (GRCm39) |
H288L |
probably damaging |
Het |
| Vmn2r45 |
A |
T |
7: 8,488,765 (GRCm39) |
N88K |
probably benign |
Het |
| Wt1 |
A |
G |
2: 105,002,666 (GRCm39) |
T511A |
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 |
|
|
R3786:Tsc1
|
UTSW |
2 |
28,577,154 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4490:Tsc1
|
UTSW |
2 |
28,560,937 (GRCm39) |
missense |
probably damaging |
0.97 |
|
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'- TCCGAGAGAAAGCATGCTGG -3'
(R):5'- TCCATCATTGGCTAGAAGAGTTTGG -3'
Sequencing Primer
(F):5'- GAGAAAGCATGCTGGCATCCTC -3'
(R):5'- TCTTGACTCGGACTCAGAAAG -3'
|
| Posted On |
2014-10-16 |
Incidental Mutation