Mutagenetix > Incidental Mutation

Incidental Mutation 'R2216:Tnnt3'

241158

Institutional Source

Beutler Lab

Gene Symbol

Tnnt3

Ensembl Gene

ENSMUSG00000061723

Gene Name

troponin T3, skeletal, fast

Synonyms

fTnT, skeletal muscle fast-twitch TnT

MMRRC Submission

040218-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R2216 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

142498836-142516009 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 142512564 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Cysteine at position 222 (Y222C)

Ref Sequence

ENSEMBL: ENSMUSP00000101578 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000074187] [ENSMUST00000078497] [ENSMUST00000105941] [ENSMUST00000105942] [ENSMUST00000105943] [ENSMUST00000105944] [ENSMUST00000105945] [ENSMUST00000105946] [ENSMUST00000105947] [ENSMUST00000105948] [ENSMUST00000105949] [ENSMUST00000105950] [ENSMUST00000179658] [ENSMUST00000105954] [ENSMUST00000105955] [ENSMUST00000105957] [ENSMUST00000146804] [ENSMUST00000180152] [ENSMUST00000169299] [ENSMUST00000105952] [ENSMUST00000105953] [ENSMUST00000105958] [ENSMUST00000128294]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000074187
AA Change: Y198C

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

SMART Domains

Protein: ENSMUSP00000073815
Gene: ENSMUSG00000061723
AA Change: Y198C

Domain	Start	End	E-Value	Type
low complexity region	4	27	N/A	INTRINSIC
Pfam:Troponin	52	194	1.5e-42	PFAM
low complexity region	233	245	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000078497
AA Change: Y218C

PolyPhen 2 Score 0.013 (Sensitivity: 0.96; Specificity: 0.78)

SMART Domains

Protein: ENSMUSP00000077587
Gene: ENSMUSG00000061723
AA Change: Y218C

Domain	Start	End	E-Value	Type
coiled coil region	1	48	N/A	INTRINSIC
Pfam:Troponin	72	214	2.1e-42	PFAM
low complexity region	253	265	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105941
AA Change: Y198C

PolyPhen 2 Score 0.009 (Sensitivity: 0.96; Specificity: 0.77)

SMART Domains

Protein: ENSMUSP00000101561
Gene: ENSMUSG00000061723
AA Change: Y198C

Domain	Start	End	E-Value	Type
low complexity region	4	27	N/A	INTRINSIC
Pfam:Troponin	52	194	2.1e-42	PFAM
low complexity region	229	245	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105942
AA Change: Y189C

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000101562
Gene: ENSMUSG00000061723
AA Change: Y189C

Domain	Start	End	E-Value	Type
low complexity region	4	18	N/A	INTRINSIC
Pfam:Troponin	43	185	1.7e-42	PFAM
low complexity region	224	236	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105943
AA Change: Y189C

PolyPhen 2 Score 0.009 (Sensitivity: 0.96; Specificity: 0.77)

SMART Domains

Protein: ENSMUSP00000101563
Gene: ENSMUSG00000061723
AA Change: Y189C

Domain	Start	End	E-Value	Type
low complexity region	4	18	N/A	INTRINSIC
Pfam:Troponin	43	185	1.9e-42	PFAM
low complexity region	220	236	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105944
AA Change: Y200C

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

SMART Domains

Protein: ENSMUSP00000101564
Gene: ENSMUSG00000061723
AA Change: Y200C

Domain	Start	End	E-Value	Type
coiled coil region	1	30	N/A	INTRINSIC
Pfam:Troponin	54	196	2e-42	PFAM
low complexity region	235	247	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105945
AA Change: Y198C

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

SMART Domains

Protein: ENSMUSP00000101565
Gene: ENSMUSG00000061723
AA Change: Y198C

Domain	Start	End	E-Value	Type
low complexity region	4	27	N/A	INTRINSIC
Pfam:Troponin	52	194	1.5e-42	PFAM
low complexity region	233	245	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105946
AA Change: Y204C

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000101566
Gene: ENSMUSG00000061723
AA Change: Y204C

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	58	200	1.8e-42	PFAM
low complexity region	235	251	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105947
AA Change: Y209C

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000101567
Gene: ENSMUSG00000061723
AA Change: Y209C

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	63	205	1.9e-42	PFAM
low complexity region	240	256	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105948
AA Change: Y200C

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000101568
Gene: ENSMUSG00000061723
AA Change: Y200C

Domain	Start	End	E-Value	Type
coiled coil region	1	30	N/A	INTRINSIC
Pfam:Troponin	54	196	2.2e-42	PFAM
low complexity region	231	247	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105949
AA Change: Y194C

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000101569
Gene: ENSMUSG00000061723
AA Change: Y194C

Domain	Start	End	E-Value	Type
low complexity region	4	23	N/A	INTRINSIC
Pfam:Troponin	48	190	1.8e-42	PFAM
low complexity region	229	241	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105950
AA Change: Y212C

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000101570
Gene: ENSMUSG00000061723
AA Change: Y212C

Domain	Start	End	E-Value	Type
coiled coil region	3	42	N/A	INTRINSIC
Pfam:Troponin	66	208	1.9e-42	PFAM
internal_repeat_1	213	240	4.67e-5	PROSPERO
low complexity region	247	259	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000179658
AA Change: Y222C

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000136278
Gene: ENSMUSG00000061723
AA Change: Y222C

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	76	212	1.5e-36	PFAM
low complexity region	257	269	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105954
AA Change: Y213C

PolyPhen 2 Score 0.013 (Sensitivity: 0.96; Specificity: 0.78)

SMART Domains

Protein: ENSMUSP00000101574
Gene: ENSMUSG00000061723
AA Change: Y213C

Domain	Start	End	E-Value	Type
coiled coil region	1	44	N/A	INTRINSIC
Pfam:Troponin	67	209	1.9e-42	PFAM
low complexity region	248	260	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105955
AA Change: Y205C

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

SMART Domains

Protein: ENSMUSP00000101575
Gene: ENSMUSG00000061723
AA Change: Y205C

Domain	Start	End	E-Value	Type
coiled coil region	1	36	N/A	INTRINSIC
Pfam:Troponin	59	201	2.2e-42	PFAM
low complexity region	240	252	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105957
AA Change: Y209C

PolyPhen 2 Score 0.028 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000101577
Gene: ENSMUSG00000061723
AA Change: Y209C

Domain	Start	End	E-Value	Type
low complexity region	4	36	N/A	INTRINSIC
Pfam:Troponin	63	205	1.8e-42	PFAM
low complexity region	244	256	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000146804
AA Change: Y195C

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

SMART Domains

Protein: ENSMUSP00000116087
Gene: ENSMUSG00000061723
AA Change: Y195C

Domain	Start	End	E-Value	Type
low complexity region	10	24	N/A	INTRINSIC
Pfam:Troponin	49	191	1.4e-40	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000180152
AA Change: Y222C

PolyPhen 2 Score 0.013 (Sensitivity: 0.96; Specificity: 0.78)

SMART Domains

Protein: ENSMUSP00000137111
Gene: ENSMUSG00000061723
AA Change: Y222C

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	76	218	5.1e-42	PFAM
internal_repeat_1	223	250	2.76e-5	PROSPERO
low complexity region	257	269	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000169299
AA Change: Y204C

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000127854
Gene: ENSMUSG00000061723
AA Change: Y204C

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	58	200	1.8e-42	PFAM
low complexity region	235	251	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105952
AA Change: Y209C

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000101572
Gene: ENSMUSG00000061723
AA Change: Y209C

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	63	205	1.8e-42	PFAM
low complexity region	244	256	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105953
AA Change: Y212C

PolyPhen 2 Score 0.013 (Sensitivity: 0.96; Specificity: 0.78)

SMART Domains

Protein: ENSMUSP00000101573
Gene: ENSMUSG00000061723
AA Change: Y212C

Domain	Start	End	E-Value	Type
coiled coil region	3	42	N/A	INTRINSIC
Pfam:Troponin	66	208	1.9e-42	PFAM
low complexity region	247	259	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105958
AA Change: Y222C

PolyPhen 2 Score 0.028 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000101578
Gene: ENSMUSG00000061723
AA Change: Y222C

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	76	218	2.1e-42	PFAM
low complexity region	253	269	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000125649

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144259

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153262

Predicted Effect

probably benign
Transcript: ENSMUST00000128294

SMART Domains

Protein: ENSMUSP00000116223
Gene: ENSMUSG00000061723

Domain	Start	End	E-Value	Type
low complexity region	4	24	N/A	INTRINSIC
Pfam:Troponin	49	107	3.6e-17	PFAM

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 97.0%
20x: 94.2%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The binding of Ca(2+) to the trimeric troponin complex initiates the process of muscle contraction. Increased Ca(2+) concentrations produce a conformational change in the troponin complex that is transmitted to tropomyosin dimers situated along actin filaments. The altered conformation permits increased interaction between a myosin head and an actin filament which, ultimately, produces a muscle contraction. The troponin complex has protein subunits C, I, and T. Subunit C binds Ca(2+) and subunit I binds to actin and inhibits actin-myosin interaction. Subunit T binds the troponin complex to the tropomyosin complex and is also required for Ca(2+)-mediated activation of actomyosin ATPase activity. There are 3 different troponin T genes that encode tissue-specific isoforms of subunit T for fast skeletal-, slow skeletal-, and cardiac-muscle. This gene encodes fast skeletal troponin T protein; also known as troponin T type 3. Alternative splicing results in multiple transcript variants encoding additional distinct troponin T type 3 isoforms. A developmentally regulated switch between fetal/neonatal and adult troponin T type 3 isoforms occurs. Additional splice variants have been described but their biological validity has not been established. Mutations in this gene may cause distal arthrogryposis multiplex congenita type 2B (DA2B). [provided by RefSeq, Oct 2009]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit neonatal lethality, decreased fetal weight, liver and kidney hemorrhage and thin diaphragm. Mice heterozygous for this allele exhibit growth retardation with mild skeleton defects. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 54 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aipl1	G	T	11: 72,031,446	P146T	probably damaging	Het
Arnt2	T	A	7: 84,275,351	T423S	probably damaging	Het
Bend5	A	G	4: 111,448,590	N277S	probably null	Het
Cd22	G	T	7: 30,867,046	T816N	probably damaging	Het
Cep126	G	A	9: 8,120,678	R115C	probably damaging	Het
Cep85	T	C	4: 134,131,430	H710R	possibly damaging	Het
Cmya5	A	T	13: 93,093,495	L1695H	probably damaging	Het
Col24a1	T	C	3: 145,314,981	V371A	probably benign	Het
Csmd1	T	A	8: 17,027,339		probably null	Het
Cyp1a1	T	A	9: 57,702,069		probably null	Het
Dennd1c	C	T	17: 57,074,492		probably null	Het
Dmxl1	G	A	18: 49,893,923	V2033I	probably benign	Het
Dtna	A	G	18: 23,569,565	H51R	probably damaging	Het
Dysf	G	A	6: 84,207,245		probably null	Het
Gcn1l1	T	A	5: 115,593,661	V945E	probably benign	Het
Gm12800	T	A	4: 101,910,060	W169R	probably damaging	Het
Gpbar1	C	G	1: 74,278,894	L99V	probably damaging	Het
Hdac9	A	T	12: 34,429,517	D212E	probably damaging	Het
Itga1	A	T	13: 114,997,029	D448E	probably benign	Het
Itga2b	T	A	11: 102,467,866	N75I	probably benign	Het
Klra7	T	C	6: 130,228,586	E117G	probably benign	Het
Kmt2b	G	A	7: 30,574,065	R2349C	probably benign	Het
Masp1	T	C	16: 23,492,055	N209S	probably benign	Het
Mybpc2	C	T	7: 44,512,500		probably null	Het
Myh15	C	G	16: 49,165,838	S1557*	probably null	Het
Myo3a	A	C	2: 22,577,771	T346P	probably benign	Het
Nim1k	A	G	13: 119,714,215	Y152H	probably damaging	Het
Nrp2	C	T	1: 62,762,918	R507*	probably null	Het
Olfr513	C	T	7: 108,755,612	T252M	probably damaging	Het
Olfr702	T	A	7: 106,823,998	H176L	probably damaging	Het
Parp14	T	C	16: 35,857,205	I798V	probably benign	Het
Pcnx2	C	T	8: 125,888,077	A212T	probably benign	Het
Pkhd1l1	A	T	15: 44,573,895	H3522L	probably damaging	Het
Pram1	C	T	17: 33,641,284	A275V	probably benign	Het
Prkag1	A	T	15: 98,815,946	M1K	probably null	Het
Prss52	T	C	14: 64,113,593	S276P	probably damaging	Het
Ranbp17	A	T	11: 33,481,125	V284D	probably damaging	Het
Reln	T	C	5: 22,048,005	D648G	probably benign	Het
Rnf112	A	G	11: 61,452,279	L190P	probably damaging	Het
Scn5a	G	T	9: 119,485,612	P2010Q	probably benign	Het
Scn5a	T	C	9: 119,513,085	Y1138C	probably benign	Het
Slc4a9	A	G	18: 36,530,745	H274R	probably benign	Het
Slc5a6	T	G	5: 31,039,335	E391D	possibly damaging	Het
Speer2	T	C	16: 69,858,842	Q32R	possibly damaging	Het
Tars	A	G	15: 11,389,708	V372A	probably benign	Het
Thsd7a	A	T	6: 12,337,268	L1250Q	possibly damaging	Het
Trim40	T	C	17: 36,888,983	I68V	probably benign	Het
Trp53tg5	T	C	2: 164,471,306	I150V	probably benign	Het
Ube2u	T	C	4: 100,532,168	V109A	probably benign	Het
Usp54	A	T	14: 20,561,840	D969E	probably benign	Het
Vil1	G	T	1: 74,425,679	R495L	probably benign	Het
Wfs1	T	A	5: 36,967,220	K700*	probably null	Het
Zcchc8	A	G	5: 123,707,403	L298P	probably damaging	Het
Zfp946	A	T	17: 22,454,716	Q150H	possibly damaging	Het

Other mutations in Tnnt3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02247:Tnnt3	APN	7	142508325	intron	probably benign
IGL02376:Tnnt3	APN	7	142512558	missense	possibly damaging	0.64
R0432:Tnnt3	UTSW	7	142512086	missense	probably benign	0.09
R0463:Tnnt3	UTSW	7	142512335	missense	probably benign	0.25
R1421:Tnnt3	UTSW	7	142511366	missense	probably damaging	0.97
R1521:Tnnt3	UTSW	7	142515825	nonsense	probably null
R1789:Tnnt3	UTSW	7	142512364	missense	probably damaging	1.00
R1990:Tnnt3	UTSW	7	142511525	missense	possibly damaging	0.78
R1991:Tnnt3	UTSW	7	142511525	missense	possibly damaging	0.78
R2029:Tnnt3	UTSW	7	142512627	splice site	probably benign
R4779:Tnnt3	UTSW	7	142514283	intron	probably benign
R5568:Tnnt3	UTSW	7	142512040	missense	probably damaging	0.98
R5756:Tnnt3	UTSW	7	142502758	critical splice donor site	probably null
R5994:Tnnt3	UTSW	7	142511266	missense	probably damaging	1.00
R6265:Tnnt3	UTSW	7	142501645	missense	probably damaging	0.98
R7658:Tnnt3	UTSW	7	142512096	nonsense	probably null
R8280:Tnnt3	UTSW	7	142501622	missense	unknown
R9074:Tnnt3	UTSW	7	142512086	missense	probably benign	0.05

Predicted Primers

PCR Primer
(F):5'- TCTTAGCGATGACAAGCTGAGG -3'
(R):5'- AGCCAGGTCTCAAGGCAAAG -3'

Sequencing Primer
(F):5'- TCCCAGATCATGCAGGGC -3'
(R):5'- GTCTCAAGGCAAAGGCATGACC -3'

Posted On

2014-10-15