Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3265 | 10018;10019;10020 | chr2:178764722;178764721;178764720 | chr2:179629449;179629448;179629447 |
| N2AB | 3265 | 10018;10019;10020 | chr2:178764722;178764721;178764720 | chr2:179629449;179629448;179629447 |
| N2A | 3265 | 10018;10019;10020 | chr2:178764722;178764721;178764720 | chr2:179629449;179629448;179629447 |
| N2B | 3219 | 9880;9881;9882 | chr2:178764722;178764721;178764720 | chr2:179629449;179629448;179629447 |
| Novex-1 | 3219 | 9880;9881;9882 | chr2:178764722;178764721;178764720 | chr2:179629449;179629448;179629447 |
| Novex-2 | 3219 | 9880;9881;9882 | chr2:178764722;178764721;178764720 | chr2:179629449;179629448;179629447 |
| Novex-3 | 3265 | 10018;10019;10020 | chr2:178764722;178764721;178764720 | chr2:179629449;179629448;179629447 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | None | None | None | N | 0.221 | 0.276 | 0.234412748748 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| R/S | rs141708467  |
-0.076 | 0.116 | N | 0.473 | 0.295 | 0.255270683199 | gnomAD-2.1.1 | 2.48E-05 | None | None | None | None | I | None | 2.40385E-04 | 2.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/S | rs141708467 |
-0.076 | 0.116 | N | 0.473 | 0.295 | 0.255270683199 | gnomAD-3.1.2 | 1.24888E-04 | None | None | None | None | I | None | 4.10331E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78469E-04 |
| R/S | rs141708467 |
-0.076 | 0.116 | N | 0.473 | 0.295 | 0.255270683199 | gnomAD-4.0.0 | 2.54036E-05 | None | None | None | None | I | None | 4.6724E-04 | 3.334E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 6.40184E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6532 | likely_pathogenic | 0.8046 | pathogenic | -0.016 | Destabilizing | 0.07 | N | 0.311 | neutral | None | None | None | None | I |
| R/C | 0.2288 | likely_benign | 0.35 | ambiguous | -0.311 | Destabilizing | 0.901 | D | 0.411 | neutral | None | None | None | None | I |
| R/D | 0.8883 | likely_pathogenic | 0.9402 | pathogenic | -0.359 | Destabilizing | 0.296 | N | 0.504 | neutral | None | None | None | None | I |
| R/E | 0.5592 | ambiguous | 0.7196 | pathogenic | -0.329 | Destabilizing | 0.08 | N | 0.443 | neutral | None | None | None | None | I |
| R/F | 0.5886 | likely_pathogenic | 0.7163 | pathogenic | -0.364 | Destabilizing | 0.174 | N | 0.521 | neutral | None | None | None | None | I |
| R/G | 0.6219 | likely_pathogenic | 0.8013 | pathogenic | -0.132 | Destabilizing | 0.116 | N | 0.459 | neutral | D | 0.538385742 | None | None | I |
| R/H | 0.1229 | likely_benign | 0.1639 | benign | -0.607 | Destabilizing | 0.901 | D | 0.424 | neutral | None | None | None | None | I |
| R/I | 0.2314 | likely_benign | 0.3775 | ambiguous | 0.243 | Stabilizing | 0.002 | N | 0.329 | neutral | N | 0.459933374 | None | None | I |
| R/K | 0.1327 | likely_benign | 0.171 | benign | -0.248 | Destabilizing | None | N | 0.221 | neutral | N | 0.438640558 | None | None | I |
| R/L | 0.2621 | likely_benign | 0.3671 | ambiguous | 0.243 | Stabilizing | None | N | 0.319 | neutral | None | None | None | None | I |
| R/M | 0.3356 | likely_benign | 0.5076 | ambiguous | -0.148 | Destabilizing | 0.596 | D | 0.469 | neutral | None | None | None | None | I |
| R/N | 0.6947 | likely_pathogenic | 0.8042 | pathogenic | -0.167 | Destabilizing | 0.296 | N | 0.477 | neutral | None | None | None | None | I |
| R/P | 0.9705 | likely_pathogenic | 0.9855 | pathogenic | 0.173 | Stabilizing | 0.46 | N | 0.525 | neutral | None | None | None | None | I |
| R/Q | 0.1271 | likely_benign | 0.1725 | benign | -0.197 | Destabilizing | 0.296 | N | 0.501 | neutral | None | None | None | None | I |
| R/S | 0.6648 | likely_pathogenic | 0.8096 | pathogenic | -0.319 | Destabilizing | 0.116 | N | 0.473 | neutral | N | 0.463311875 | None | None | I |
| R/T | 0.3893 | ambiguous | 0.6023 | pathogenic | -0.196 | Destabilizing | 0.116 | N | 0.429 | neutral | N | 0.474503566 | None | None | I |
| R/V | 0.3831 | ambiguous | 0.5165 | ambiguous | 0.173 | Stabilizing | 0.001 | N | 0.328 | neutral | None | None | None | None | I |
| R/W | 0.2421 | likely_benign | 0.3611 | ambiguous | -0.569 | Destabilizing | 0.972 | D | 0.411 | neutral | None | None | None | None | I |
| R/Y | 0.397 | ambiguous | 0.5085 | ambiguous | -0.177 | Destabilizing | 0.46 | N | 0.479 | 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.