Mutagenetix > Incidental Mutation

Incidental Mutation 'R0605:Tsc1'

55623

Institutional Source

Beutler Lab

Gene Symbol

Tsc1

Ensembl Gene

ENSMUSG00000026812

Gene Name

tuberous sclerosis 1

Synonyms

hamartin

MMRRC Submission

038794-MU

Accession Numbers

Ncbi RefSeq: NM_022887.3; MGI: 1929183

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0605 (G1)

Quality Score

168

Status

Validated

Chromosome

Chromosomal Location

28641228-28691167 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 28671778 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Phenylalanine at position 309 (S309F)

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: S309F

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

SMART Domains

Protein: ENSMUSP00000028155
Gene: ENSMUSG00000026812
AA Change: S309F

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: S309F

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

SMART Domains

Protein: ENSMUSP00000109498
Gene: ENSMUSG00000026812
AA Change: S309F

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: S309F

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

SMART Domains

Protein: ENSMUSP00000109500
Gene: ENSMUSG00000026812
AA Change: S309F

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: S309F

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

SMART Domains

Protein: ENSMUSP00000109501
Gene: ENSMUSG00000026812
AA Change: S309F

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: S309F

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

SMART Domains

Protein: ENSMUSP00000120888
Gene: ENSMUSG00000026812
AA Change: S309F

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

possibly damaging
Transcript: ENSMUST00000156857
AA Change: S309F

PolyPhen 2 Score 0.856 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000115380
Gene: ENSMUSG00000026812
AA Change: S309F

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

Meta Mutation Damage Score

0.3361

Coding Region Coverage

1x: 99.4%
3x: 98.9%
10x: 97.6%
20x: 95.4%

Validation Efficiency

100% (85/85)

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: 84 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4933406P04Rik	G	A	10: 20,311,227		probably benign	Het
Adam28	A	T	14: 68,606,600		probably benign	Het
Adamts3	A	G	5: 89,861,475	W110R	possibly damaging	Het
Add1	T	C	5: 34,614,224	V342A	possibly damaging	Het
Aff3	A	G	1: 38,209,987	S680P	probably damaging	Het
Ak9	T	C	10: 41,345,139	Y322H	probably damaging	Het
Als2	A	G	1: 59,168,414	L1528S	probably benign	Het
Ass1	A	T	2: 31,514,819	N371Y	probably damaging	Het
Atp6v1a	A	C	16: 44,111,496		probably null	Het
Bpi	T	C	2: 158,261,394	L103P	probably damaging	Het
Cd80	G	A	16: 38,482,694	V168I	probably benign	Het
Cfh	T	C	1: 140,102,358	S926G	probably damaging	Het
Chrd	A	T	16: 20,735,439	T304S	probably damaging	Het
Chsy3	A	G	18: 59,409,053	Y421C	probably damaging	Het
Cmbl	T	G	15: 31,585,309	V101G	probably damaging	Het
Colgalt2	T	A	1: 152,495,792		probably benign	Het
Coq4	C	T	2: 29,789,998	Q101*	probably null	Het
Cr2	T	C	1: 195,163,596		probably benign	Het
Cry1	T	C	10: 85,184,359	D38G	probably damaging	Het
Dmxl2	T	C	9: 54,419,945	D758G	probably benign	Het
Epsti1	C	T	14: 77,927,237		probably benign	Het
Fam24b	T	C	7: 131,327,186		probably benign	Het
Fem1c	G	A	18: 46,505,160	R592C	probably benign	Het
Foxred1	T	C	9: 35,204,882	Y490C	possibly damaging	Het
Gm14124	A	G	2: 150,268,603	I404M	unknown	Het
Gm9875	A	G	2: 13,557,888	K9R	unknown	Het
Grid2ip	T	C	5: 143,379,362	S322P	probably damaging	Het
Gucy1b2	A	G	14: 62,403,159		probably benign	Het
Hmcn1	A	T	1: 150,657,376		probably null	Het
Hpdl	C	T	4: 116,820,787	S159N	possibly damaging	Het
Hsd17b12	A	T	2: 94,033,642	M285K	probably benign	Het
Icam5	T	C	9: 21,032,197	I23T	probably benign	Het
Kat5	A	G	19: 5,608,336		probably benign	Het
Lama3	A	G	18: 12,506,949	N67S	probably benign	Het
Lamb2	T	C	9: 108,486,105		probably benign	Het
Lgals3bp	A	G	11: 118,393,394	F453S	probably damaging	Het
Lypd4	A	G	7: 24,865,375	Y113H	probably damaging	Het
Mdm1	C	T	10: 118,146,601	T47M	probably damaging	Het
Mei1	C	A	15: 82,070,150	T52K	probably benign	Het
Meiob	G	A	17: 24,818,262		probably benign	Het
Ndufaf6	A	G	4: 11,051,224	V292A	probably damaging	Het
Neb	T	A	2: 52,264,026	M2358L	possibly damaging	Het
Nlrp1b	A	G	11: 71,156,179	S1119P	possibly damaging	Het
Nsmaf	A	G	4: 6,418,470		probably null	Het
Ogfod1	T	C	8: 94,047,267		probably benign	Het
Olfr1097	T	C	2: 86,890,419	Y252C	possibly damaging	Het
Olfr1410	G	T	1: 92,607,896	V20L	probably benign	Het
Olfr291	T	C	7: 84,857,137	I256T	probably damaging	Het
Osbpl1a	T	A	18: 12,882,279		probably null	Het
Otud7b	T	A	3: 96,144,959		probably benign	Het
P3h3	T	A	6: 124,856,035	H185L	probably damaging	Het
P4htm	G	A	9: 108,583,724	A183V	probably null	Het
Peak1	C	T	9: 56,227,098		probably benign	Het
Phf20l1	A	G	15: 66,595,122	K88R	probably damaging	Het
Phlpp2	A	G	8: 109,933,211	N721S	probably benign	Het
Plagl2	T	C	2: 153,235,944	K39R	probably benign	Het
Plppr1	A	T	4: 49,323,466	N252I	probably damaging	Het
Pom121l2	C	T	13: 21,982,036	A159V	probably damaging	Het
Prom2	C	A	2: 127,539,995		probably null	Het
Prrc2c	T	C	1: 162,682,426	T1017A	probably damaging	Het
Rimbp3	G	T	16: 17,211,699	A996S	probably damaging	Het
Rnf213	A	G	11: 119,431,717	T1387A	probably benign	Het
Scaper	A	T	9: 55,815,518		probably benign	Het
Scara5	A	G	14: 65,759,648	E403G	possibly damaging	Het
Scrib	T	C	15: 76,067,553	I94V	possibly damaging	Het
Shank3	T	C	15: 89,524,147	F67L	possibly damaging	Het
Shprh	T	C	10: 11,207,112	F1562L	probably damaging	Het
Src	C	T	2: 157,469,921	T529M	probably damaging	Het
Sycp2l	T	A	13: 41,143,466	M341K	probably benign	Het
Syde1	T	C	10: 78,589,095		probably benign	Het
Tarsl2	A	T	7: 65,678,071	R509S	probably damaging	Het
Tle6	T	A	10: 81,594,346	H324L	probably damaging	Het
Tnfaip8	ACTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC	ACTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC	18: 50,046,845		probably benign	Het
Tnfrsf14	T	A	4: 154,925,380	K115*	probably null	Het
Trappc10	T	C	10: 78,201,497	N824S	possibly damaging	Het
Ttc21a	A	G	9: 119,961,842	I885V	possibly damaging	Het
Ttn	C	T	2: 76,740,453	A26699T	probably damaging	Het
Ttn	T	C	2: 76,948,371	Y1262C	unknown	Het
Usp49	T	C	17: 47,674,926		probably null	Het
Vmn1r226	A	T	17: 20,687,871	T122S	probably benign	Het
Vps8	A	T	16: 21,559,337	T1033S	probably benign	Het
Vwf	C	A	6: 125,685,837	T2728K	probably benign	Het
Wdr5b	T	C	16: 36,041,996	S162P	probably benign	Het
Xrn1	C	T	9: 96,026,877	Q1235*	probably null	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
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
R8021:Tsc1	UTSW	2	28686889	missense	possibly damaging	0.67
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'- ACTTTGTTCCCAGGGATGGCTAGG -3'
(R):5'- CGCGAGACAAGTTGCATTTCAGG -3'

Sequencing Primer
(F):5'- CTAGGAGCCAACGGTTTTAAGC -3'
(R):5'- GGGTCCTCCTGAAACTTACACTG -3'

Posted On

2013-07-11