Mutagenetix > Incidental Mutation

Incidental Mutation 'R4707:Tsc1'

355279

Institutional Source

Beutler Lab

Gene Symbol

Tsc1

Ensembl Gene

ENSMUSG00000026812

Gene Name

TSC complex subunit 1

Synonyms

tuberous sclerosis 1, hamartin

MMRRC Submission

041955-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4707 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

28531240-28581179 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 28562419 bp (GRCm39)

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]

AlphaFold

Q9EP53

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

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: 9,224,544 (GRCm39)	K450R	probably damaging	Het
Abcd2	T	C	15: 91,043,385 (GRCm39)	D601G	probably benign	Het
Abcf3	A	G	16: 20,367,808 (GRCm39)	K56E	possibly damaging	Het
Acaca	T	C	11: 84,203,680 (GRCm39)	V1477A	probably damaging	Het
Adamts20	G	A	15: 94,231,528 (GRCm39)	P887L	possibly damaging	Het
Ahnak	T	G	19: 8,994,099 (GRCm39)	S5128A	probably benign	Het
Ahsa2	C	A	11: 23,443,162 (GRCm39)	V197F	probably benign	Het
Ak9	C	A	10: 41,221,456 (GRCm39)	H402N	probably benign	Het
Alpk1	G	T	3: 127,481,241 (GRCm39)	N175K	possibly damaging	Het
Als2	A	G	1: 59,254,472 (GRCm39)	V295A	probably benign	Het
Ankrd16	A	G	2: 11,783,608 (GRCm39)	D70G	probably damaging	Het
Apob	A	T	12: 8,056,205 (GRCm39)	K1562N	probably damaging	Het
Arfgap2	C	A	2: 91,100,316 (GRCm39)	S250R	probably damaging	Het
Arhgef10l	C	T	4: 140,264,194 (GRCm39)	M671I	possibly damaging	Het
Atrnl1	A	G	19: 57,617,590 (GRCm39)	I122V	probably damaging	Het
B4galnt2	C	T	11: 95,766,923 (GRCm39)		probably null	Het
C8a	A	G	4: 104,713,618 (GRCm39)	Y171H	probably damaging	Het
Cacnb4	A	G	2: 52,364,927 (GRCm39)	V112A	probably benign	Het
Capn9	G	T	8: 125,340,195 (GRCm39)	C566F	possibly damaging	Het
Ccdc88a	T	A	11: 29,397,956 (GRCm39)	S230T	probably benign	Het
Cd300c2	A	T	11: 114,887,811 (GRCm39)	F197Y	probably benign	Het
Chd5	A	G	4: 152,445,039 (GRCm39)	Y340C	probably damaging	Het
Chrd	A	T	16: 20,557,558 (GRCm39)	I726F	possibly damaging	Het
Chrna10	G	A	7: 101,762,426 (GRCm39)	P255S	possibly damaging	Het
Clasp1	T	A	1: 118,470,927 (GRCm39)	Y197*	probably null	Het
Cyp2c69	C	G	19: 39,837,852 (GRCm39)	G410A	probably benign	Het
Cyp2e1	G	A	7: 140,343,821 (GRCm39)	V20I	possibly damaging	Het
Dapp1	T	C	3: 137,638,928 (GRCm39)	D225G	probably benign	Het
Dnah5	A	T	15: 28,372,521 (GRCm39)	D2924V	probably damaging	Het
Efcab12	A	T	6: 115,791,510 (GRCm39)	L554Q	possibly damaging	Het
Emsy	T	C	7: 98,246,311 (GRCm39)	T228A	possibly damaging	Het
Evc2	G	A	5: 37,579,204 (GRCm39)	V1106I	probably benign	Het
Exoc8	G	T	8: 125,624,209 (GRCm39)	Q53K	possibly damaging	Het
Fbn2	A	T	18: 58,189,344 (GRCm39)	V1594D	probably damaging	Het
Fer1l4	T	C	2: 155,887,543 (GRCm39)	Y551C	possibly damaging	Het
Fhip1a	G	T	3: 85,595,877 (GRCm39)	T115K	probably damaging	Het
Fmnl3	A	G	15: 99,221,362 (GRCm39)	M481T	probably benign	Het
Fras1	A	G	5: 96,883,097 (GRCm39)	N2543S	probably damaging	Het
Fsd2	T	C	7: 81,209,428 (GRCm39)	D138G	probably damaging	Het
Gda	C	T	19: 21,405,992 (GRCm39)	V5I	probably benign	Het
Glt8d2	A	T	10: 82,496,583 (GRCm39)	D158E	probably damaging	Het
Gpx6	C	T	13: 21,496,434 (GRCm39)	Q3*	probably null	Het
Greb1l	A	G	18: 10,532,922 (GRCm39)	M830V	probably benign	Het
Hnrnpul1	A	C	7: 25,426,258 (GRCm39)	V531G	probably damaging	Het
Ifi206	A	T	1: 173,308,432 (GRCm39)	H521Q	probably benign	Het
Igsf3	G	C	3: 101,365,410 (GRCm39)	R1127P	probably benign	Het
Il1rl1	A	G	1: 40,489,348 (GRCm39)	R367G	probably damaging	Het
Islr	T	C	9: 58,064,970 (GRCm39)	D179G	possibly damaging	Het
Jcad	G	T	18: 4,649,338 (GRCm39)	E70*	probably null	Het
Kcnd2	T	C	6: 21,723,211 (GRCm39)	I467T	probably benign	Het
Lrrc27	A	G	7: 138,822,614 (GRCm39)	T502A	probably benign	Het
Lrrtm3	T	A	10: 63,923,781 (GRCm39)	H462L	probably benign	Het
Mbd5	T	C	2: 49,140,168 (GRCm39)	L44S	probably damaging	Het
Mccc1	C	A	3: 36,030,022 (GRCm39)	M429I	probably damaging	Het
Mgam	A	T	6: 40,691,566 (GRCm39)		probably null	Het
Mipep	T	A	14: 61,109,552 (GRCm39)	I643N	probably damaging	Het
Mmrn1	A	T	6: 60,965,457 (GRCm39)	I1162L	probably benign	Het
Mrc2	G	A	11: 105,239,257 (GRCm39)		probably null	Het
Mug1	G	A	6: 121,861,600 (GRCm39)	C1354Y	probably damaging	Het
Nbeal2	A	T	9: 110,461,123 (GRCm39)	S1647T	probably benign	Het
Ndufaf2	C	G	13: 108,189,314 (GRCm39)	A145P	probably damaging	Het
Nedd9	A	T	13: 41,492,051 (GRCm39)		probably null	Het
Nr4a2	T	A	2: 57,002,105 (GRCm39)	H116L	probably benign	Het
Nwd2	A	G	5: 63,951,665 (GRCm39)	Y232C	probably damaging	Het
Odf4	A	G	11: 68,817,514 (GRCm39)	L58P	probably damaging	Het
Or2a20	T	A	6: 43,193,883 (GRCm39)	V12D	probably benign	Het
Or4a27	T	A	2: 88,559,056 (GRCm39)	M296L	possibly damaging	Het
Or4c116	A	T	2: 88,942,576 (GRCm39)	F93L	probably damaging	Het
Or4g17	T	A	2: 111,209,990 (GRCm39)	L215H	probably damaging	Het
Or7e165	C	T	9: 19,694,596 (GRCm39)	H18Y	probably damaging	Het
Or8g24	A	G	9: 38,989,558 (GRCm39)	V161A	probably benign	Het
Or8s5	G	T	15: 98,238,659 (GRCm39)	H70Q	possibly damaging	Het
Orc6	T	A	8: 86,029,579 (GRCm39)	I41K	probably damaging	Het
Pikfyve	A	G	1: 65,307,005 (GRCm39)	T1798A	probably benign	Het
Prdx6b	T	C	2: 80,123,404 (GRCm39)	L71P	probably damaging	Het
Prmt2	A	G	10: 76,062,055 (GRCm39)	I50T	probably damaging	Het
Ptdss1	T	C	13: 67,143,482 (GRCm39)		probably null	Het
Pygl	T	C	12: 70,254,532 (GRCm39)	T138A	possibly damaging	Het
Rab3c	T	C	13: 110,198,434 (GRCm39)	E198G	probably benign	Het
Rbl2	A	G	8: 91,812,196 (GRCm39)	Y255C	probably damaging	Het
Rev3l	T	A	10: 39,699,393 (GRCm39)	S1297T	probably damaging	Het
Rgma	C	A	7: 73,067,564 (GRCm39)	T367K	probably damaging	Het
Rps6ka5	C	T	12: 100,564,144 (GRCm39)		probably null	Het
Rslcan18	A	T	13: 67,246,590 (GRCm39)	C217S	probably damaging	Het
Rtp3	A	G	9: 110,815,279 (GRCm39)		probably benign	Het
Ryr1	A	T	7: 28,745,087 (GRCm39)	N3848K	probably damaging	Het
Sema6a	T	A	18: 47,381,779 (GRCm39)	T923S	probably benign	Het
Serpinb6d	A	T	13: 33,855,336 (GRCm39)	T337S	possibly damaging	Het
Sf3b1	G	A	1: 55,029,666 (GRCm39)	T1112M	probably damaging	Het
Shroom3	G	T	5: 93,090,945 (GRCm39)	V1151F	probably damaging	Het
Sidt1	A	T	16: 44,090,221 (GRCm39)	Y369*	probably null	Het
Slc16a6	A	G	11: 109,354,193 (GRCm39)	S59P	probably benign	Het
Slc25a17	A	C	15: 81,211,527 (GRCm39)	L163W	probably damaging	Het
Slc44a3	T	C	3: 121,320,723 (GRCm39)	T93A	possibly damaging	Het
Sptbn1	T	C	11: 30,087,197 (GRCm39)	T1081A	possibly damaging	Het
Sptbn4	T	C	7: 27,116,431 (GRCm39)	D456G	probably benign	Het
Sycp1	C	A	3: 102,760,805 (GRCm39)	A703S	possibly damaging	Het
Tas2r118	T	A	6: 23,969,225 (GRCm39)	M279L	probably benign	Het
Tc2n	T	G	12: 101,660,832 (GRCm39)	Q133H	probably benign	Het
Tctn1	A	G	5: 122,399,468 (GRCm39)		probably null	Het
Tenm4	A	C	7: 96,423,253 (GRCm39)	K683Q	probably damaging	Het
Tex10	A	T	4: 48,468,984 (GRCm39)	S64T	probably benign	Het
Tex15	A	G	8: 34,072,525 (GRCm39)	T2691A	probably benign	Het
Tmem175	A	T	5: 108,790,016 (GRCm39)	T123S	probably damaging	Het
Ttll4	A	T	1: 74,718,166 (GRCm39)	T6S	possibly damaging	Het
Ttll8	A	T	15: 88,801,293 (GRCm39)	I465N	probably damaging	Het
Ubr3	A	G	2: 69,768,714 (GRCm39)		probably benign	Het
Ugdh	A	T	5: 65,580,695 (GRCm39)		probably null	Het
Usp34	T	C	11: 23,437,215 (GRCm39)	L3326S	probably damaging	Het
Vmn2r125	A	T	4: 156,702,276 (GRCm39)	I21F	probably damaging	Het
Vps9d1	G	A	8: 123,975,351 (GRCm39)		probably benign	Het
Xab2	G	A	8: 3,668,117 (GRCm39)	R154C	possibly damaging	Het
Zbtb12	T	C	17: 35,114,475 (GRCm39)	S87P	probably damaging	Het
Zc3h12a	A	G	4: 125,014,686 (GRCm39)	M266T	probably damaging	Het
Zfp108	G	A	7: 23,959,837 (GRCm39)	A143T	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
R4490:Tsc1	UTSW	2	28,560,937 (GRCm39)	missense	probably damaging	0.97
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'- CAACTTGTCTCGCGGTAAAG -3'
(R):5'- AAGTTTATTACTGCCACATAGCCC -3'

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

Posted On

2015-10-21