Mutagenetix > Incidental Mutation

Incidental Mutation 'R8021:Tsc1'

617339

Institutional Source

Beutler Lab

Gene Symbol

Tsc1

Ensembl Gene

ENSMUSG00000026812

Gene Name

tuberous sclerosis 1

Synonyms

hamartin

MMRRC Submission

067460-MU

Accession Numbers

Ncbi RefSeq: NM_022887.3; MGI: 1929183

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8021 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

28641228-28691167 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 28686889 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Phenylalanine at position 1068 (I1068F)

Ref Sequence

ENSEMBL: ENSMUSP00000109500 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028155] [ENSMUST00000113867] [ENSMUST00000113869] [ENSMUST00000113870] [ENSMUST00000133565]

AlphaFold

Q9EP53

Predicted Effect

possibly damaging
Transcript: ENSMUST00000028155
AA Change: I1067F

PolyPhen 2 Score 0.777 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000028155
Gene: ENSMUSG00000026812
AA Change: I1067F

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

possibly damaging
Transcript: ENSMUST00000113867
AA Change: I1062F

PolyPhen 2 Score 0.777 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000109498
Gene: ENSMUSG00000026812
AA Change: I1062F

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

possibly damaging
Transcript: ENSMUST00000113869
AA Change: I1068F

PolyPhen 2 Score 0.669 (Sensitivity: 0.86; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000109500
Gene: ENSMUSG00000026812
AA Change: I1068F

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

possibly damaging
Transcript: ENSMUST00000113870
AA Change: I1067F

PolyPhen 2 Score 0.777 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000109501
Gene: ENSMUSG00000026812
AA Change: I1067F

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: ENSMUST00000133565

SMART Domains

Protein: ENSMUSP00000120888
Gene: ENSMUSG00000026812

Domain	Start	End	E-Value	Type
Pfam:Hamartin	2	455	1.3e-198	PFAM

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

97% (74/76)

MGI Phenotype

Strain: 2183900
Lethality: E10-E12
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: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1810010H24Rik	A	G	11: 107,025,927	I12V	unknown	Het
9130011E15Rik	C	T	19: 45,956,741		probably null	Het
A630010A05Rik	C	T	16: 14,589,246	T13I		Het
Acsm5	A	G	7: 119,542,393	E537G	possibly damaging	Het
Adam25	C	A	8: 40,754,759	A354E	probably damaging	Het
Adamts3	T	C	5: 89,683,184	K1004E	possibly damaging	Het
Ap3d1	C	A	10: 80,714,301	V699L	probably benign	Het
Arel1	T	G	12: 84,934,958	H216P	possibly damaging	Het
Armc12	T	A	17: 28,530,905	F8I	probably benign	Het
Ascc3	T	A	10: 50,731,648	M1416K	probably benign	Het
Catsperb	A	C	12: 101,588,063	N672T	probably benign	Het
Ccdc30	T	C	4: 119,352,679	H291R	probably benign	Het
Cd33	A	G	7: 43,528,838	V371A	unknown	Het
Cpt1b	A	T	15: 89,421,426	M362K	probably benign	Het
Dusp5	T	A	19: 53,529,498	S61T	probably benign	Het
Eogt	T	G	6: 97,134,330	D190A	probably damaging	Het
Fat3	T	A	9: 15,999,109	I1866F	probably damaging	Het
Fer1l4	T	A	2: 156,022,591	I1668F	probably damaging	Het
Foxn3	A	T	12: 99,388,902	M1K	probably null	Het
Frs3	T	A	17: 47,703,114	V244E	probably damaging	Het
Gm8765	A	G	13: 50,701,094	N256S	possibly damaging	Het
Grik1	C	T	16: 87,914,222	V832I		Het
Gtf2ird2	T	A	5: 134,203,334	V242E	probably benign	Het
Gtpbp2	C	T	17: 46,164,269	R97C	possibly damaging	Het
Habp2	T	A	19: 56,314,053	V263E	probably benign	Het
Iars2	T	A	1: 185,322,457	I337L	probably benign	Het
Ifi204	T	C	1: 173,759,353		probably benign	Het
Itih2	T	C	2: 10,105,652	T543A	probably benign	Het
Kdm2b	A	G	5: 122,932,919	S372P	probably damaging	Het
Kit	T	A	5: 75,615,491	V311E	possibly damaging	Het
Kmt2c	C	G	5: 25,287,119	V4230L	possibly damaging	Het
Lao1	T	C	4: 118,968,477	I498T	probably damaging	Het
Lrp1	G	T	10: 127,548,346	D3641E	possibly damaging	Het
Mapk8ip1	A	T	2: 92,386,415	S477T	possibly damaging	Het
Mast3	C	T	8: 70,788,252	G218S	probably benign	Het
Mical1	T	C	10: 41,482,724	V546A	probably damaging	Het
Nck2	T	C	1: 43,554,260	V209A	probably benign	Het
Ndufs4	A	G	13: 114,307,815		probably null	Het
Nek3	C	T	8: 22,157,190	V139M	probably damaging	Het
Olfr1417	T	C	19: 11,828,892	I45V	probably benign	Het
Olfr863-ps1	A	C	9: 19,942,079	Y120*	probably null	Het
Olfr877	T	A	9: 37,855,296	H159Q	probably damaging	Het
Olfr994	A	T	2: 85,430,652	M59K	probably damaging	Het
Otog	A	T	7: 46,267,342	N901I	probably damaging	Het
Pclo	A	C	5: 14,539,784	Q699H	unknown	Het
Pcnx	C	T	12: 81,918,819	R59*	probably null	Het
Pde12	A	T	14: 26,665,699	Y551*	probably null	Het
Pigg	A	G	5: 108,319,939	D268G	probably damaging	Het
Ppp1r21	A	G	17: 88,549,507	D130G	probably benign	Het
Psip1	T	C	4: 83,459,955	T435A	possibly damaging	Het
Rad54l2	T	C	9: 106,719,641	S189G	probably benign	Het
Rgs14	T	C	13: 55,383,756	C498R	probably damaging	Het
Ripply3	C	A	16: 94,328,510	A5E	probably benign	Het
Rps6ka4	T	C	19: 6,830,409	D676G	probably benign	Het
Rsbn1	T	C	3: 103,928,582	L312S	possibly damaging	Het
Secisbp2	T	A	13: 51,665,628	*415R	probably null	Het
Sephs1	T	A	2: 4,906,623	F336Y	probably benign	Het
Setdb2	A	T	14: 59,423,384	Y103*	probably null	Het
Slit2	T	A	5: 48,302,492	C1371*	probably null	Het
Stab2	C	T	10: 86,905,539	A1239T	possibly damaging	Het
Taf4b	T	A	18: 14,804,524	V218E	probably damaging	Het
Tars2	T	C	3: 95,747,514	N393S	probably benign	Het
Tbc1d30	A	G	10: 121,267,543	M528T	probably benign	Het
Tchp	A	G	5: 114,718,417	E363G	probably damaging	Het
Tec	T	A	5: 72,757,469	N568I	probably benign	Het
Ticam1	A	G	17: 56,270,089	S669P	unknown	Het
Tnk1	A	G	11: 69,854,984	S372P	probably benign	Het
Tnpo2	G	A	8: 85,055,206	A847T	probably damaging	Het
Ttc14	T	A	3: 33,809,121	Y559*	probably null	Het
Ttc41	C	A	10: 86,733,714	T652N	probably benign	Het
Tut1	T	A	19: 8,955,509	S69T	probably benign	Het
Uck1	T	C	2: 32,259,917	S40G	probably benign	Het
Vmn2r76	G	A	7: 86,225,750	T673I	probably damaging	Het
Vps13d	G	T	4: 145,148,675	P1760H		Het
Zbp1	T	C	2: 173,209,210	N289S	possibly damaging	Het
Zc3hav1l	C	A	6: 38,297,947		probably benign	Het
Zzef1	A	T	11: 72,823,416	D244V	probably damaging	Het

Other mutations in Tsc1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00333:Tsc1	APN	2	28661611	missense	probably damaging	0.98
IGL00770:Tsc1	APN	2	28665011	missense	probably damaging	1.00
IGL00774:Tsc1	APN	2	28665011	missense	probably damaging	1.00
IGL00835:Tsc1	APN	2	28672466	missense	possibly damaging	0.93
IGL00971:Tsc1	APN	2	28670940	nonsense	probably null
IGL01808:Tsc1	APN	2	28662507	missense	probably damaging	1.00
IGL02281:Tsc1	APN	2	28663595	missense	probably damaging	1.00
IGL03068:Tsc1	APN	2	28681258	missense	probably damaging	1.00
Cassava	UTSW	2	28671886	splice site	probably null
R0077:Tsc1	UTSW	2	28678943	splice site	probably benign
R0149:Tsc1	UTSW	2	28670901	missense	probably damaging	0.99
R0605:Tsc1	UTSW	2	28671778	missense	probably damaging	1.00
R0737:Tsc1	UTSW	2	28670930	missense	possibly damaging	0.94
R1199:Tsc1	UTSW	2	28665626	missense	probably damaging	1.00
R1751:Tsc1	UTSW	2	28676026	missense	probably damaging	0.97
R1757:Tsc1	UTSW	2	28686113	missense	probably benign	0.05
R1807:Tsc1	UTSW	2	28686113	missense	probably benign	0.05
R2014:Tsc1	UTSW	2	28665637	splice site	probably benign
R2284:Tsc1	UTSW	2	28665097	missense	possibly damaging	0.85
R3786:Tsc1	UTSW	2	28687142	missense	probably damaging	1.00
R4490:Tsc1	UTSW	2	28670925	missense	probably damaging	0.97
R4707:Tsc1	UTSW	2	28672407	missense	probably damaging	1.00
R4751:Tsc1	UTSW	2	28679081	missense	probably damaging	0.96
R4794:Tsc1	UTSW	2	28661690	splice site	probably null
R4906:Tsc1	UTSW	2	28675189	missense	possibly damaging	0.81
R5020:Tsc1	UTSW	2	28676519	missense	probably damaging	1.00
R5401:Tsc1	UTSW	2	28686908	nonsense	probably null
R5708:Tsc1	UTSW	2	28665185	intron	probably benign
R6435:Tsc1	UTSW	2	28676452	missense	probably benign	0.08
R6469:Tsc1	UTSW	2	28671886	splice site	probably null
R6502:Tsc1	UTSW	2	28665601	missense	probably damaging	1.00
R6617:Tsc1	UTSW	2	28686989	missense	possibly damaging	0.82
R7098:Tsc1	UTSW	2	28675732	missense	probably benign	0.00
R7503:Tsc1	UTSW	2	28687076	missense	possibly damaging	0.50
R7608:Tsc1	UTSW	2	28658736	missense	probably benign	0.01
R7677:Tsc1	UTSW	2	28672817	missense	probably benign	0.11
R7791:Tsc1	UTSW	2	28681948	missense	probably damaging	1.00
R8203:Tsc1	UTSW	2	28672995	splice site	probably null
R8228:Tsc1	UTSW	2	28676129	missense	probably benign	0.23
R9057:Tsc1	UTSW	2	28685862	missense	probably damaging	1.00
R9088:Tsc1	UTSW	2	28662605	missense	possibly damaging	0.94
R9201:Tsc1	UTSW	2	28686779	missense	probably benign
R9386:Tsc1	UTSW	2	28671846	missense	probably benign
R9731:Tsc1	UTSW	2	28676474	missense	probably benign	0.00
R9780:Tsc1	UTSW	2	28675749	missense	probably damaging	0.98

Predicted Primers

PCR Primer
(F):5'- TGCACAGATTCCTTGGTAGG -3'
(R):5'- TGTGGGGCATCTAGACTCAG -3'

Sequencing Primer
(F):5'- CATAATGAAGAGGCTTCTGGTCAC -3'
(R):5'- CATCTAGACTCAGGGAAGTCTTG -3'

Posted On

2020-01-23