Mutagenetix > Incidental Mutation

Incidental Mutation 'R7098:Tsc1'

550612

Institutional Source

Beutler Lab

Gene Symbol

Tsc1

Ensembl Gene

ENSMUSG00000026812

Gene Name

TSC complex subunit 1

Synonyms

tuberous sclerosis 1, hamartin

MMRRC Submission

045190-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7098 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

28531240-28581179 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 28565744 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Phenylalanine at position 465 (S465F)

Ref Sequence

ENSEMBL: ENSMUSP00000109500 (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: S464F

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000028155
Gene: ENSMUSG00000026812
AA Change: S464F

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: S464F

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000109498
Gene: ENSMUSG00000026812
AA Change: S464F

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: S465F

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)

SMART Domains

Protein: ENSMUSP00000109500
Gene: ENSMUSG00000026812
AA Change: S465F

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: S464F

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000109501
Gene: ENSMUSG00000026812
AA Change: S464F

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

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: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.0%

Validation Efficiency

100% (78/78)

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: 78 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A430033K04Rik	T	A	5: 138,644,784 (GRCm39)	M223K	probably benign	Het
Abce1	T	C	8: 80,412,678 (GRCm39)	T550A	probably benign	Het
Acoxl	C	T	2: 127,696,835 (GRCm39)	Q28*	probably null	Het
Adam8	T	C	7: 139,559,412 (GRCm39)	K820R	possibly damaging	Het
Adamts3	G	T	5: 90,009,354 (GRCm39)	A103D	probably damaging	Het
Apba2	T	A	7: 64,386,696 (GRCm39)	V441D	probably damaging	Het
Arap2	A	G	5: 62,833,293 (GRCm39)		probably null	Het
Arhgef10l	T	A	4: 140,308,222 (GRCm39)	M44L	probably benign	Het
Asb4	T	C	6: 5,398,499 (GRCm39)	C155R	probably damaging	Het
Bpifb6	A	T	2: 153,748,810 (GRCm39)	K269*	probably null	Het
Cc2d2a	A	T	5: 43,840,481 (GRCm39)	T161S	probably benign	Het
Ccdc15	T	A	9: 37,255,256 (GRCm39)	Q98L	probably damaging	Het
Col19a1	A	G	1: 24,565,555 (GRCm39)	S259P	unknown	Het
Col5a2	A	T	1: 45,419,227 (GRCm39)	D1284E	possibly damaging	Het
Cyp2c70	T	C	19: 40,168,931 (GRCm39)	T119A	probably benign	Het
Dennd6b	C	T	15: 89,072,890 (GRCm39)	C188Y	probably damaging	Het
Dhx8	T	A	11: 101,628,594 (GRCm39)		probably null	Het
Dhx9	T	C	1: 153,340,768 (GRCm39)	K624R	probably benign	Het
Dpys	C	T	15: 39,656,727 (GRCm39)	V447M	probably damaging	Het
E130308A19Rik	T	C	4: 59,753,004 (GRCm39)	S706P	possibly damaging	Het
Esrrb	A	G	12: 86,517,189 (GRCm39)	D107G	probably benign	Het
Frmd4a	T	C	2: 4,577,244 (GRCm39)	S367P	probably damaging	Het
Garin2	G	A	12: 78,766,408 (GRCm39)		probably null	Het
Gdi1	G	A	X: 73,350,461 (GRCm39)	R55H	probably benign	Het
Gm136	T	C	4: 34,746,628 (GRCm39)	I128V	probably benign	Het
Gm6525	T	A	3: 84,082,309 (GRCm39)	C77S	possibly damaging	Het
Grid2ip	T	C	5: 143,343,346 (GRCm39)	F14S	probably damaging	Het
Hdhd3	C	T	4: 62,418,152 (GRCm39)	R8H	probably damaging	Het
Kdelr1	C	A	7: 45,523,480 (GRCm39)	A69D	possibly damaging	Het
Krtap16-3	T	A	16: 88,759,560 (GRCm39)	Y51F	unknown	Het
Lrrc40	T	A	3: 157,747,276 (GRCm39)	N129K	probably benign	Het
Man1b1	T	A	2: 25,228,196 (GRCm39)	D155E	probably damaging	Het
Mcm5	T	C	8: 75,847,529 (GRCm39)	V442A	probably damaging	Het
Mfsd14a	C	T	3: 116,435,361 (GRCm39)	A235T	probably benign	Het
Mmp1a	C	A	9: 7,475,938 (GRCm39)	T401K	probably benign	Het
Mpig6b	C	T	17: 35,283,320 (GRCm39)	R196Q	unknown	Het
Mroh1	C	T	15: 76,292,657 (GRCm39)	Q262*	probably null	Het
Msh3	A	T	13: 92,410,619 (GRCm39)	D656E	possibly damaging	Het
Muc4	A	T	16: 32,577,465 (GRCm39)	T252S		Het
Myh15	C	T	16: 48,997,420 (GRCm39)	A1746V	possibly damaging	Het
Myh8	C	A	11: 67,169,879 (GRCm39)	T66K	probably benign	Het
Nemf	A	T	12: 69,359,241 (GRCm39)	Y999N	probably damaging	Het
Neurod1	T	C	2: 79,285,029 (GRCm39)	N118S	probably damaging	Het
Nlrp1b	T	A	11: 71,109,100 (GRCm39)	I134L	possibly damaging	Het
Nsun7	A	T	5: 66,418,326 (GRCm39)	I19F	probably damaging	Het
Ofcc1	A	G	13: 40,157,442 (GRCm39)		probably null	Het
P2rx7	A	G	5: 122,811,856 (GRCm39)	E389G	probably damaging	Het
Pam	C	T	1: 97,826,072 (GRCm39)	R194H	probably benign	Het
Pcnt	A	G	10: 76,220,673 (GRCm39)	S2052P	probably benign	Het
Pfkfb4	T	A	9: 108,828,222 (GRCm39)	Y86N	probably benign	Het
Plcd3	T	A	11: 102,968,689 (GRCm39)	D334V	probably damaging	Het
Ppard	T	C	17: 28,517,787 (GRCm39)	V285A	possibly damaging	Het
Prune2	A	G	19: 17,097,966 (GRCm39)	S1157G	probably benign	Het
Psg21	A	T	7: 18,386,470 (GRCm39)	L172H	probably damaging	Het
Psme4	C	A	11: 30,800,661 (GRCm39)	T1417K	probably damaging	Het
Ptprc	T	C	1: 138,027,423 (GRCm39)	D336G	probably benign	Het
Ralgapa1	A	T	12: 55,837,095 (GRCm39)		probably null	Het
Rap1gap	C	A	4: 137,443,393 (GRCm39)		probably null	Het
Scap	T	C	9: 110,201,310 (GRCm39)	S100P	possibly damaging	Het
Scpep1	T	C	11: 88,820,011 (GRCm39)	I426V	possibly damaging	Het
Sdk1	T	C	5: 142,082,625 (GRCm39)	I1341T	probably damaging	Het
Sfmbt2	T	A	2: 10,584,000 (GRCm39)	Y786N	probably benign	Het
Sh3tc1	A	T	5: 35,859,358 (GRCm39)		probably null	Het
Slc5a5	T	A	8: 71,341,182 (GRCm39)	I386F	probably damaging	Het
Smarca4	T	G	9: 21,546,116 (GRCm39)	M98R	probably benign	Het
St18	G	A	1: 6,898,066 (GRCm39)	D623N	probably damaging	Het
Sult2a1	A	T	7: 13,549,978 (GRCm39)		probably null	Het
Tgfb2	C	T	1: 186,362,834 (GRCm39)	R330H	probably damaging	Het
Thoc3	A	G	13: 54,614,119 (GRCm39)	I168T	probably damaging	Het
Tmem126a	C	T	7: 90,100,062 (GRCm39)	M160I	possibly damaging	Het
Tmem200b	C	T	4: 131,649,704 (GRCm39)	P208L	probably benign	Het
Tnrc6c	T	C	11: 117,604,952 (GRCm39)	V29A	probably benign	Het
Ttll5	A	G	12: 85,964,447 (GRCm39)		probably null	Het
Unc13d	G	T	11: 115,954,552 (GRCm39)	L1019I	probably damaging	Het
Vmn2r102	A	T	17: 19,914,670 (GRCm39)	H745L	probably damaging	Het
Wars2	T	G	3: 99,123,957 (GRCm39)	S273A	probably damaging	Het
Xrcc6	C	A	15: 81,919,955 (GRCm39)	S498*	probably null	Het
Ybx1	A	T	4: 119,140,050 (GRCm39)	N92K	possibly damaging	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
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
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'- TGCTCATCTGGAAGAACTGTTG -3'
(R):5'- TAAACACTCAGCCAGGCGAG -3'

Sequencing Primer
(F):5'- CATCTGGAAGAACTGTTGCCGATG -3'
(R):5'- CGTTTGTGCACTACAGGGAAC -3'

Posted On

2019-05-15