Incidental Mutation 'D3080:Tnnc1'
ID129
Institutional Source Beutler Lab
Gene Symbol Tnnc1
Ensembl Gene ENSMUSG00000091898
Gene Nametroponin C, cardiac/slow skeletal
SynonymscTnC, TnC
Accession Numbers

Genbank: NM_009393; MGI: 98779

Is this an essential gene? Possibly non essential (E-score: 0.389) question?
Stock #D3080 of strain grasshopper
Quality Score
Status Validated
Chromosome14
Chromosomal Location31208312-31211729 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) C to A at 31210190 bp
ZygosityHomozygous
Amino Acid Change Aspartic acid to Glutamic Acid at position 62 (D62E)
Ref Sequence ENSEMBL: ENSMUSP00000131991 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000022469] [ENSMUST00000164989] [ENSMUST00000165981] [ENSMUST00000169169] [ENSMUST00000170268] [ENSMUST00000171735] [ENSMUST00000172142]
Predicted Effect probably benign
Transcript: ENSMUST00000022469
SMART Domains Protein: ENSMUSP00000022469
Gene: ENSMUSG00000021910

DomainStartEndE-ValueType
PX 15 119 2.17e-26 SMART
PDB:4PQ8|A 287 420 9e-8 PDB
SCOP:d1h6ta2 291 421 6e-29 SMART
Blast:LRR 311 332 5e-6 BLAST
Blast:LRR 333 355 6e-6 BLAST
Blast:LRR 378 403 5e-7 BLAST
Blast:LRR 403 429 6e-7 BLAST
low complexity region 489 501 N/A INTRINSIC
low complexity region 517 534 N/A INTRINSIC
coiled coil region 625 650 N/A INTRINSIC
low complexity region 662 695 N/A INTRINSIC
low complexity region 1038 1069 N/A INTRINSIC
low complexity region 1081 1193 N/A INTRINSIC
low complexity region 1491 1509 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000161399
Predicted Effect noncoding transcript
Transcript: ENSMUST00000164617
Predicted Effect probably benign
Transcript: ENSMUST00000164989
SMART Domains Protein: ENSMUSP00000126982
Gene: ENSMUSG00000021910

DomainStartEndE-ValueType
PX 15 119 2.17e-26 SMART
Pfam:LRR_4 289 332 3.2e-8 PFAM
Pfam:LRR_1 290 311 2.9e-3 PFAM
Pfam:LRR_1 313 332 4.2e-2 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000165981
SMART Domains Protein: ENSMUSP00000130210
Gene: ENSMUSG00000021910

DomainStartEndE-ValueType
PX 15 119 2.17e-26 SMART
Pfam:LRR_7 289 305 7.4e-2 PFAM
Pfam:LRR_6 289 309 3.8e-2 PFAM
Pfam:LRR_4 289 333 5.9e-8 PFAM
Pfam:LRR_8 289 346 6.8e-10 PFAM
Pfam:LRR_1 290 311 4.4e-3 PFAM
Pfam:LRR_8 312 369 7.3e-9 PFAM
Pfam:LRR_1 313 333 1.8e-2 PFAM
Pfam:LRR_4 329 377 2.3e-8 PFAM
Pfam:LRR_6 333 354 2e-3 PFAM
Pfam:LRR_7 334 350 1.9e-1 PFAM
Pfam:LRR_1 335 354 1.2e-2 PFAM
Blast:LRR 378 403 1e-6 BLAST
Blast:LRR 403 429 1e-7 BLAST
Predicted Effect noncoding transcript
Transcript: ENSMUST00000167602
Predicted Effect probably damaging
Transcript: ENSMUST00000169169
AA Change: D62E

PolyPhen 2 Score 0.981 (Sensitivity: 0.75; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000131991
Gene: ENSMUSG00000091898
AA Change: D62E

DomainStartEndE-ValueType
EFh 19 48 1.08e2 SMART
EFh 56 84 2.39e-8 SMART
EFh 96 124 2.7e-7 SMART
EFh 132 160 4.03e-6 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000170268
AA Change: D62E

PolyPhen 2 Score 0.010 (Sensitivity: 0.96; Specificity: 0.77)
SMART Domains Protein: ENSMUSP00000128765
Gene: ENSMUSG00000091898
AA Change: D62E

DomainStartEndE-ValueType
EFh 19 48 1.08e2 SMART
EFh 56 84 2.39e-8 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000171735
SMART Domains Protein: ENSMUSP00000127132
Gene: ENSMUSG00000021910

DomainStartEndE-ValueType
PX 15 119 2.17e-26 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000172142
SMART Domains Protein: ENSMUSP00000132413
Gene: ENSMUSG00000021910

DomainStartEndE-ValueType
PX 15 119 2.17e-26 SMART
Pfam:LRR_7 289 305 8.2e-2 PFAM
Pfam:LRR_6 289 309 4.2e-2 PFAM
Pfam:LRR_4 289 333 6.6e-8 PFAM
Pfam:LRR_8 289 346 7.6e-10 PFAM
Pfam:LRR_1 290 311 4.9e-3 PFAM
Pfam:LRR_8 312 369 7.7e-9 PFAM
Pfam:LRR_1 313 333 2e-2 PFAM
Pfam:LRR_4 329 377 2.7e-8 PFAM
Pfam:LRR_6 333 354 2.2e-3 PFAM
Pfam:LRR_7 334 350 2.1e-1 PFAM
Pfam:LRR_1 335 354 1.3e-2 PFAM
Blast:LRR 378 403 1e-6 BLAST
Blast:LRR 403 429 1e-7 BLAST
low complexity region 489 501 N/A INTRINSIC
Meta Mutation Damage Score 0.6467 question?
Coding Region Coverage
  • 1x: 88.9%
  • 3x: 76.7%
Validation Efficiency 82% (141/173)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Troponin is a central regulatory protein of striated muscle contraction, and together with tropomyosin, is located on the actin filament. Troponin consists of 3 subunits: TnI, which is the inhibitor of actomyosin ATPase; TnT, which contains the binding site for tropomyosin; and TnC, the protein encoded by this gene. The binding of calcium to TnC abolishes the inhibitory action of TnI, thus allowing the interaction of actin with myosin, the hydrolysis of ATP, and the generation of tension. Mutations in this gene are associated with cardiomyopathy dilated type 1Z. [provided by RefSeq, Oct 2008]
Allele List at MGI

All alleles(2) : Targeted, other(2)

Other mutations in this stock
Total: 20 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2310003L06Rik C A 5: 87,971,987 P201Q possibly damaging Het
Bdp1 A T 13: 100,023,621 S2417R probably benign Het
Dscaml1 A T 9: 45,684,325 H783L probably benign Het
Fbxl5 A T 5: 43,758,366 M568K probably benign Het
Gab1 T A 8: 80,766,378 D710V probably damaging Homo
Gabrr2 T C 4: 33,084,466 F128S probably damaging Het
Gm8251 C A 1: 44,067,335 Het
Hyou1 T A 9: 44,384,477 V343E probably damaging Het
Nlrp4a A G 7: 26,444,341 T44A probably benign Het
Nsd3 C A 8: 25,713,545 T1362N possibly damaging Homo
Olfr523 G A 7: 140,176,362 V81M possibly damaging Het
Pcm1 T A 8: 41,275,939 N649K probably damaging Homo
Pde4dip T C 3: 97,766,830 K257E probably damaging Het
Pfpl G A 19: 12,428,832 R149Q probably damaging Homo
Pou2f2 G T 7: 25,097,133 probably benign Het
Rptn A G 3: 93,395,828 D156G possibly damaging Het
Sec31a T C 5: 100,363,832 D1107G probably damaging Het
Smyd3 A G 1: 179,086,422 Y239H probably damaging Het
Stoml3 T C 3: 53,497,994 F32S probably benign Het
Vsig10 C T 5: 117,343,819 A358V probably damaging Het
Other mutations in Tnnc1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02188:Tnnc1 APN 14 31210660 missense possibly damaging 0.80
IGL03308:Tnnc1 APN 14 31209841 unclassified probably benign
R0110:Tnnc1 UTSW 14 31211408 missense probably damaging 1.00
R0469:Tnnc1 UTSW 14 31211408 missense probably damaging 1.00
R8557:Tnnc1 UTSW 14 31210605 missense probably damaging 0.99
Nature of Mutation
DNA sequencing using the SOLiD technique identified a C to A transversion at position 229 of the Tcnn1transcript in exon 3 of 6 total exons. The mutated nucleotide causes an aspartic acid to glutamic acid substitution at amino acid 62 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Tcnn1gene encodes a 161 amino acid protein that is a component of troponin (Tn), the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments. Tn-C contains four calcium-binding EF hands (Uniprot P19123). 
 
The D62E change occurs in the second EF-hand, but is predicted to be probably benign by the PolyPhen program.
Posted On2010-03-12