Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35314 | 106165;106166;106167 | chr2:178530675;178530674;178530673 | chr2:179395402;179395401;179395400 |
| N2AB | 33673 | 101242;101243;101244 | chr2:178530675;178530674;178530673 | chr2:179395402;179395401;179395400 |
| N2A | 32746 | 98461;98462;98463 | chr2:178530675;178530674;178530673 | chr2:179395402;179395401;179395400 |
| N2B | 26249 | 78970;78971;78972 | chr2:178530675;178530674;178530673 | chr2:179395402;179395401;179395400 |
| Novex-1 | 26374 | 79345;79346;79347 | chr2:178530675;178530674;178530673 | chr2:179395402;179395401;179395400 |
| Novex-2 | 26441 | 79546;79547;79548 | chr2:178530675;178530674;178530673 | chr2:179395402;179395401;179395400 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs377171054  |
-0.577 | 0.183 | N | 0.217 | 0.059 | None | gnomAD-2.1.1 | 8.2E-05 | None | None | None | None | I | None | 0 | 2.26283E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.16924E-04 | 0 |
| A/T | rs377171054 |
-0.577 | 0.183 | N | 0.217 | 0.059 | None | gnomAD-3.1.2 | 1.05158E-04 | None | None | None | None | I | None | 7.24E-05 | 6.55E-05 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 1.61693E-04 | 0 | 0 |
| A/T | rs377171054 |
-0.577 | 0.183 | N | 0.217 | 0.059 | None | gnomAD-4.0.0 | 9.29458E-05 | None | None | None | None | I | None | 4.00513E-05 | 1.33342E-04 | None | 0 | 0 | None | 1.5623E-05 | 1.64366E-04 | 1.11027E-04 | 0 | 9.60584E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5456 | ambiguous | 0.5424 | ambiguous | -0.806 | Destabilizing | 0.836 | D | 0.407 | neutral | None | None | None | None | I |
| A/D | 0.3925 | ambiguous | 0.412 | ambiguous | -0.434 | Destabilizing | 0.836 | D | 0.503 | neutral | None | None | None | None | I |
| A/E | 0.3198 | likely_benign | 0.3362 | benign | -0.507 | Destabilizing | 0.523 | D | 0.471 | neutral | N | 0.483609372 | None | None | I |
| A/F | 0.4975 | ambiguous | 0.4799 | ambiguous | -0.735 | Destabilizing | 0.716 | D | 0.509 | neutral | None | None | None | None | I |
| A/G | 0.1477 | likely_benign | 0.1506 | benign | -0.691 | Destabilizing | 0.001 | N | 0.085 | neutral | N | 0.516647297 | None | None | I |
| A/H | 0.6709 | likely_pathogenic | 0.6832 | pathogenic | -0.772 | Destabilizing | 0.983 | D | 0.506 | neutral | None | None | None | None | I |
| A/I | 0.3419 | ambiguous | 0.3353 | benign | -0.163 | Destabilizing | 0.001 | N | 0.161 | neutral | None | None | None | None | I |
| A/K | 0.6297 | likely_pathogenic | 0.6588 | pathogenic | -0.911 | Destabilizing | 0.593 | D | 0.472 | neutral | None | None | None | None | I |
| A/L | 0.2779 | likely_benign | 0.2818 | benign | -0.163 | Destabilizing | None | N | 0.15 | neutral | None | None | None | None | I |
| A/M | 0.3623 | ambiguous | 0.3444 | ambiguous | -0.31 | Destabilizing | 0.716 | D | 0.484 | neutral | None | None | None | None | I |
| A/N | 0.3639 | ambiguous | 0.3792 | ambiguous | -0.557 | Destabilizing | 0.716 | D | 0.511 | neutral | None | None | None | None | I |
| A/P | 0.2378 | likely_benign | 0.3234 | benign | -0.235 | Destabilizing | 0.921 | D | 0.481 | neutral | N | 0.470624219 | None | None | I |
| A/Q | 0.4683 | ambiguous | 0.4877 | ambiguous | -0.71 | Destabilizing | 0.94 | D | 0.479 | neutral | None | None | None | None | I |
| A/R | 0.5543 | ambiguous | 0.5752 | pathogenic | -0.574 | Destabilizing | 0.836 | D | 0.48 | neutral | None | None | None | None | I |
| A/S | 0.1075 | likely_benign | 0.1082 | benign | -0.893 | Destabilizing | 0.183 | N | 0.224 | neutral | N | 0.495674592 | None | None | I |
| A/T | 0.1168 | likely_benign | 0.115 | benign | -0.861 | Destabilizing | 0.183 | N | 0.217 | neutral | N | 0.482051934 | None | None | I |
| A/V | 0.1577 | likely_benign | 0.1578 | benign | -0.235 | Destabilizing | None | N | 0.122 | neutral | N | 0.499426973 | None | None | I |
| A/W | 0.8268 | likely_pathogenic | 0.8267 | pathogenic | -0.988 | Destabilizing | 0.983 | D | 0.534 | neutral | None | None | None | None | I |
| A/Y | 0.6403 | likely_pathogenic | 0.6283 | pathogenic | -0.604 | Destabilizing | 0.836 | D | 0.52 | neutral | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.