Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2665 | 8218;8219;8220 | chr2:178771334;178771333;178771332 | chr2:179636061;179636060;179636059 |
| N2AB | 2665 | 8218;8219;8220 | chr2:178771334;178771333;178771332 | chr2:179636061;179636060;179636059 |
| N2A | 2665 | 8218;8219;8220 | chr2:178771334;178771333;178771332 | chr2:179636061;179636060;179636059 |
| N2B | 2619 | 8080;8081;8082 | chr2:178771334;178771333;178771332 | chr2:179636061;179636060;179636059 |
| Novex-1 | 2619 | 8080;8081;8082 | chr2:178771334;178771333;178771332 | chr2:179636061;179636060;179636059 |
| Novex-2 | 2619 | 8080;8081;8082 | chr2:178771334;178771333;178771332 | chr2:179636061;179636060;179636059 |
| Novex-3 | 2665 | 8218;8219;8220 | chr2:178771334;178771333;178771332 | chr2:179636061;179636060;179636059 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs751461803  |
-1.074 | 0.171 | D | 0.473 | 0.207 | 0.408444019923 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.8E-06 | 0 |
| I/M | rs751461803 |
-1.074 | 0.171 | D | 0.473 | 0.207 | 0.408444019923 | gnomAD-4.0.0 | 1.5906E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85656E-06 | 0 | 0 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3081 | likely_benign | 0.3358 | benign | -2.288 | Highly Destabilizing | 0.007 | N | 0.278 | neutral | None | None | None | None | N |
| I/C | 0.4839 | ambiguous | 0.5161 | ambiguous | -1.592 | Destabilizing | None | N | 0.282 | neutral | None | None | None | None | N |
| I/D | 0.6337 | likely_pathogenic | 0.6128 | pathogenic | -2.02 | Highly Destabilizing | 0.072 | N | 0.57 | neutral | None | None | None | None | N |
| I/E | 0.5003 | ambiguous | 0.4945 | ambiguous | -1.875 | Destabilizing | 0.072 | N | 0.546 | neutral | None | None | None | None | N |
| I/F | 0.0973 | likely_benign | 0.099 | benign | -1.423 | Destabilizing | None | N | 0.207 | neutral | N | 0.505333644 | None | None | N |
| I/G | 0.5573 | ambiguous | 0.5679 | pathogenic | -2.767 | Highly Destabilizing | 0.072 | N | 0.488 | neutral | None | None | None | None | N |
| I/H | 0.3393 | likely_benign | 0.3421 | ambiguous | -2.058 | Highly Destabilizing | 0.214 | N | 0.527 | neutral | None | None | None | None | N |
| I/K | 0.3374 | likely_benign | 0.3224 | benign | -1.728 | Destabilizing | 0.072 | N | 0.542 | neutral | None | None | None | None | N |
| I/L | 0.0981 | likely_benign | 0.0988 | benign | -0.952 | Destabilizing | None | N | 0.118 | neutral | N | 0.507372444 | None | None | N |
| I/M | 0.0981 | likely_benign | 0.1007 | benign | -0.819 | Destabilizing | 0.171 | N | 0.473 | neutral | D | 0.537704962 | None | None | N |
| I/N | 0.235 | likely_benign | 0.2293 | benign | -1.84 | Destabilizing | 0.055 | N | 0.596 | neutral | D | 0.679185609 | None | None | N |
| I/P | 0.8208 | likely_pathogenic | 0.7814 | pathogenic | -1.372 | Destabilizing | 0.356 | N | 0.593 | neutral | None | None | None | None | N |
| I/Q | 0.3392 | likely_benign | 0.3394 | benign | -1.822 | Destabilizing | 0.356 | N | 0.573 | neutral | None | None | None | None | N |
| I/R | 0.2509 | likely_benign | 0.2326 | benign | -1.29 | Destabilizing | 0.214 | N | 0.577 | neutral | None | None | None | None | N |
| I/S | 0.2457 | likely_benign | 0.2519 | benign | -2.583 | Highly Destabilizing | 0.012 | N | 0.39 | neutral | D | 0.574253241 | None | None | N |
| I/T | 0.176 | likely_benign | 0.191 | benign | -2.299 | Highly Destabilizing | None | N | 0.206 | neutral | D | 0.556126603 | None | None | N |
| I/V | 0.0736 | likely_benign | 0.0759 | benign | -1.372 | Destabilizing | None | N | 0.13 | neutral | N | 0.473596815 | None | None | N |
| I/W | 0.5894 | likely_pathogenic | 0.5973 | pathogenic | -1.679 | Destabilizing | 0.356 | N | 0.522 | neutral | None | None | None | None | N |
| I/Y | 0.2817 | likely_benign | 0.2798 | benign | -1.411 | Destabilizing | None | N | 0.221 | neutral | None | None | None | None | N |
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.