Mutagenetix > Incidental Mutations

Incidental Mutation 'R4707:Tsc1'

355279

Institutional Source

Beutler Lab

Gene Symbol

Tsc1

Ensembl Gene

ENSMUSG00000026812

Gene Name

tuberous sclerosis 1

Synonyms

hamartin

MMRRC Submission

041955-MU

Accession Numbers

Ncbi RefSeq: NM_022887.3; MGI: 1929183

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R4707 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

28641228-28691167 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 28672407 bp

Zygosity

Heterozygous

Amino Acid Change

Serine to Arginine at position 348 (S348R)

Ref Sequence

ENSEMBL: ENSMUSP00000109501 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028155] [ENSMUST00000113867] [ENSMUST00000113869] [ENSMUST00000113870] [ENSMUST00000133565] [ENSMUST00000156857]

Predicted Effect

probably damaging
Transcript: ENSMUST00000028155
AA Change: S348R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000028155
Gene: ENSMUSG00000026812
AA Change: S348R

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 damaging
Transcript: ENSMUST00000113867
AA Change: S348R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000109498
Gene: ENSMUSG00000026812
AA Change: S348R

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 damaging
Transcript: ENSMUST00000113869
AA Change: S348R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000109500
Gene: ENSMUSG00000026812
AA Change: S348R

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 damaging
Transcript: ENSMUST00000113870
AA Change: S348R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000109501
Gene: ENSMUSG00000026812
AA Change: S348R

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: S348R

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000120888
Gene: ENSMUSG00000026812
AA Change: S348R

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000139642

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153625

Predicted Effect

probably benign
Transcript: ENSMUST00000156857

SMART Domains

Protein: ENSMUSP00000115380
Gene: ENSMUSG00000026812

Domain	Start	End	E-Value	Type
Pfam:Hamartin	2	348	2.3e-170	PFAM

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.0%
20x: 94.7%

Validation Efficiency

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: 115 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700010I14Rik	A	G	17: 9,005,712	K450R	probably damaging	Het
Abcd2	T	C	15: 91,159,182	D601G	probably benign	Het
Abcf3	A	G	16: 20,549,058	K56E	possibly damaging	Het
Acaca	T	C	11: 84,312,854	V1477A	probably damaging	Het
Adamts20	G	A	15: 94,333,647	P887L	possibly damaging	Het
Ahnak	T	G	19: 9,016,735	S5128A	probably benign	Het
Ahsa2	C	A	11: 23,493,162	V197F	probably benign	Het
Ak9	C	A	10: 41,345,460	H402N	probably benign	Het
Alpk1	G	T	3: 127,687,592	N175K	possibly damaging	Het
Als2	A	G	1: 59,215,313	V295A	probably benign	Het
Ankrd16	A	G	2: 11,778,797	D70G	probably damaging	Het
Apob	A	T	12: 8,006,205	K1562N	probably damaging	Het
Arfgap2	C	A	2: 91,269,971	S250R	probably damaging	Het
Arhgef10l	C	T	4: 140,536,883	M671I	possibly damaging	Het
Atrnl1	A	G	19: 57,629,158	I122V	probably damaging	Het
B4galnt2	C	T	11: 95,876,097		probably null	Het
C8a	A	G	4: 104,856,421	Y171H	probably damaging	Het
Cacnb4	A	G	2: 52,474,915	V112A	probably benign	Het
Capn9	G	T	8: 124,613,456	C566F	possibly damaging	Het
Ccdc88a	T	A	11: 29,447,956	S230T	probably benign	Het
Cd300c2	A	T	11: 114,996,985	F197Y	probably benign	Het
Chd5	A	G	4: 152,360,582	Y340C	probably damaging	Het
Chrd	A	T	16: 20,738,808	I726F	possibly damaging	Het
Chrna10	G	A	7: 102,113,219	P255S	possibly damaging	Het
Clasp1	T	A	1: 118,543,197	Y197*	probably null	Het
Cyp2c69	C	G	19: 39,849,408	G410A	probably benign	Het
Cyp2e1	G	A	7: 140,763,908	V20I	possibly damaging	Het
Dapp1	T	C	3: 137,933,167	D225G	probably benign	Het
Dnah5	A	T	15: 28,372,375	D2924V	probably damaging	Het
Efcab12	A	T	6: 115,814,549	L554Q	possibly damaging	Het
Emsy	T	C	7: 98,597,104	T228A	possibly damaging	Het
Evc2	G	A	5: 37,421,860	V1106I	probably benign	Het
Exoc8	G	T	8: 124,897,470	Q53K	possibly damaging	Het
Fam160a1	G	T	3: 85,688,570	T115K	probably damaging	Het
Fbn2	A	T	18: 58,056,272	V1594D	probably damaging	Het
Fer1l4	T	C	2: 156,045,623	Y551C	possibly damaging	Het
Fmnl3	A	G	15: 99,323,481	M481T	probably benign	Het
Fras1	A	G	5: 96,735,238	N2543S	probably damaging	Het
Fsd2	T	C	7: 81,559,680	D138G	probably damaging	Het
Gda	C	T	19: 21,428,628	V5I	probably benign	Het
Glt8d2	A	T	10: 82,660,749	D158E	probably damaging	Het
Gpx6	C	T	13: 21,312,264	Q3*	probably null	Het
Greb1l	A	G	18: 10,532,922	M830V	probably benign	Het
Hnrnpul1	A	C	7: 25,726,833	V531G	probably damaging	Het
Ifi206	A	T	1: 173,480,866	H521Q	probably benign	Het
Igsf3	G	C	3: 101,458,094	R1127P	probably benign	Het
Il1rl1	A	G	1: 40,450,188	R367G	probably damaging	Het
Islr	T	C	9: 58,157,687	D179G	possibly damaging	Het
Jcad	G	T	18: 4,649,338	E70*	probably null	Het
Kcnd2	T	C	6: 21,723,212	I467T	probably benign	Het
Lrrc27	A	G	7: 139,242,698	T502A	probably benign	Het
Lrrtm3	T	A	10: 64,088,002	H462L	probably benign	Het
Mbd5	T	C	2: 49,250,156	L44S	probably damaging	Het
Mccc1	C	A	3: 35,975,873	M429I	probably damaging	Het
Mgam	A	T	6: 40,714,632		probably null	Het
Mipep	T	A	14: 60,872,103	I643N	probably damaging	Het
Mmrn1	A	T	6: 60,988,473	I1162L	probably benign	Het
Mrc2	G	A	11: 105,348,431		probably null	Het
Mug1	G	A	6: 121,884,641	C1354Y	probably damaging	Het
Nbeal2	A	T	9: 110,632,055	S1647T	probably benign	Het
Ndufaf2	C	G	13: 108,052,780	A145P	probably damaging	Het
Nedd9	A	T	13: 41,338,575		probably null	Het
Nr4a2	T	A	2: 57,112,093	H116L	probably benign	Het
Nwd2	A	G	5: 63,794,322	Y232C	probably damaging	Het
Odf4	A	G	11: 68,926,688	L58P	probably damaging	Het
Olfr1197	T	A	2: 88,728,712	M296L	possibly damaging	Het
Olfr1221	A	T	2: 89,112,232	F93L	probably damaging	Het
Olfr1284	T	A	2: 111,379,645	L215H	probably damaging	Het
Olfr284	G	T	15: 98,340,778	H70Q	possibly damaging	Het
Olfr434	T	A	6: 43,216,949	V12D	probably benign	Het
Olfr58	C	T	9: 19,783,300	H18Y	probably damaging	Het
Olfr938	A	G	9: 39,078,262	V161A	probably benign	Het
Orc6	T	A	8: 85,302,950	I41K	probably damaging	Het
Pikfyve	A	G	1: 65,267,846	T1798A	probably benign	Het
Prdx6b	T	C	2: 80,293,060	L71P	probably damaging	Het
Prmt2	A	G	10: 76,226,221	I50T	probably damaging	Het
Ptdss1	T	C	13: 66,995,418		probably null	Het
Pygl	T	C	12: 70,207,758	T138A	possibly damaging	Het
Rab3c	T	C	13: 110,061,900	E198G	probably benign	Het
Rbl2	A	G	8: 91,085,568	Y255C	probably damaging	Het
Rev3l	T	A	10: 39,823,397	S1297T	probably damaging	Het
Rgma	C	A	7: 73,417,816	T367K	probably damaging	Het
Rps6ka5	C	T	12: 100,597,885		probably null	Het
Rslcan18	A	T	13: 67,098,526	C217S	probably damaging	Het
Rtp3	A	G	9: 110,986,211		probably benign	Het
Ryr1	A	T	7: 29,045,662	N3848K	probably damaging	Het
Sema6a	T	A	18: 47,248,712	T923S	probably benign	Het
Serpinb6d	A	T	13: 33,671,353	T337S	possibly damaging	Het
Sf3b1	G	A	1: 54,990,507	T1112M	probably damaging	Het
Shroom3	G	T	5: 92,943,086	V1151F	probably damaging	Het
Sidt1	A	T	16: 44,269,858	Y369*	probably null	Het
Slc16a6	A	G	11: 109,463,367	S59P	probably benign	Het
Slc25a17	A	C	15: 81,327,326	L163W	probably damaging	Het
Slc44a3	T	C	3: 121,527,074	T93A	possibly damaging	Het
Sptbn1	T	C	11: 30,137,197	T1081A	possibly damaging	Het
Sptbn4	T	C	7: 27,417,006	D456G	probably benign	Het
Sycp1	C	A	3: 102,853,489	A703S	possibly damaging	Het
Tas2r118	T	A	6: 23,969,226	M279L	probably benign	Het
Tc2n	T	G	12: 101,694,573	Q133H	probably benign	Het
Tctn1	A	G	5: 122,261,405		probably null	Het
Tenm4	A	C	7: 96,774,046	K683Q	probably damaging	Het
Tex10	A	T	4: 48,468,984	S64T	probably benign	Het
Tex15	A	G	8: 33,582,497	T2691A	probably benign	Het
Tmem175	A	T	5: 108,642,150	T123S	probably damaging	Het
Ttll4	A	T	1: 74,679,007	T6S	possibly damaging	Het
Ttll8	A	T	15: 88,917,090	I465N	probably damaging	Het
Ubr3	A	G	2: 69,938,370		probably benign	Het
Ugdh	A	T	5: 65,423,352		probably null	Het
Usp34	T	C	11: 23,487,215	L3326S	probably damaging	Het
Vmn2r125	A	T	4: 156,349,981	I21F	probably damaging	Het
Vps9d1	G	A	8: 123,248,612		probably benign	Het
Xab2	G	A	8: 3,618,117	R154C	possibly damaging	Het
Zbtb12	T	C	17: 34,895,499	S87P	probably damaging	Het
Zc3h12a	A	G	4: 125,120,893	M266T	probably damaging	Het
Zfp108	G	A	7: 24,260,412	A143T	probably benign	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
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

Predicted Primers

PCR Primer
(F):5'- CAACTTGTCTCGCGGTAAAG -3'
(R):5'- AAGTTTATTACTGCCACATAGCCC -3'

Sequencing Primer
(F):5'- CAGATTTCTGAGTTCAAGGCCAGC -3'
(R):5'- TGCCACATAGCCCCCAGAG -3'

Posted On

2015-10-21