Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32412 | 97459;97460;97461 | chr2:178542522;178542521;178542520 | chr2:179407249;179407248;179407247 |
| N2AB | 30771 | 92536;92537;92538 | chr2:178542522;178542521;178542520 | chr2:179407249;179407248;179407247 |
| N2A | 29844 | 89755;89756;89757 | chr2:178542522;178542521;178542520 | chr2:179407249;179407248;179407247 |
| N2B | 23347 | 70264;70265;70266 | chr2:178542522;178542521;178542520 | chr2:179407249;179407248;179407247 |
| Novex-1 | 23472 | 70639;70640;70641 | chr2:178542522;178542521;178542520 | chr2:179407249;179407248;179407247 |
| Novex-2 | 23539 | 70840;70841;70842 | chr2:178542522;178542521;178542520 | chr2:179407249;179407248;179407247 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs761246419  |
-1.264 | 0.684 | N | 0.361 | 0.267 | 0.605904737968 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 5.81E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| I/T | rs761246419 |
-1.264 | 0.684 | N | 0.361 | 0.267 | 0.605904737968 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs761246419 |
-1.264 | 0.684 | N | 0.361 | 0.267 | 0.605904737968 | gnomAD-4.0.0 | 1.30348E-05 | None | None | None | None | N | None | 1.33572E-05 | 1.00063E-04 | None | 0 | 0 | None | 0 | 0 | 1.18885E-05 | 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 | 0.1984 | likely_benign | 0.1503 | benign | -1.721 | Destabilizing | 0.373 | N | 0.377 | neutral | None | None | None | None | N |
| I/C | 0.5964 | likely_pathogenic | 0.5273 | ambiguous | -1.737 | Destabilizing | 0.996 | D | 0.308 | neutral | None | None | None | None | N |
| I/D | 0.7154 | likely_pathogenic | 0.6582 | pathogenic | -1.456 | Destabilizing | 0.835 | D | 0.454 | neutral | None | None | None | None | N |
| I/E | 0.4878 | ambiguous | 0.4411 | ambiguous | -1.443 | Destabilizing | 0.742 | D | 0.461 | neutral | None | None | None | None | N |
| I/F | 0.2573 | likely_benign | 0.2173 | benign | -1.488 | Destabilizing | 0.884 | D | 0.377 | neutral | N | 0.476919101 | None | None | N |
| I/G | 0.6507 | likely_pathogenic | 0.5409 | ambiguous | -2.02 | Highly Destabilizing | 0.742 | D | 0.455 | neutral | None | None | None | None | N |
| I/H | 0.5959 | likely_pathogenic | 0.5105 | ambiguous | -1.291 | Destabilizing | 0.987 | D | 0.404 | neutral | None | None | None | None | N |
| I/K | 0.3489 | ambiguous | 0.2793 | benign | -1.13 | Destabilizing | 0.91 | D | 0.455 | neutral | None | None | None | None | N |
| I/L | 0.1661 | likely_benign | 0.1478 | benign | -0.966 | Destabilizing | 0.164 | N | 0.24 | neutral | N | 0.467547351 | None | None | N |
| I/M | 0.0987 | likely_benign | 0.0854 | benign | -1.013 | Destabilizing | 0.939 | D | 0.391 | neutral | N | 0.490148284 | None | None | N |
| I/N | 0.353 | ambiguous | 0.2888 | benign | -1.081 | Destabilizing | 0.028 | N | 0.325 | neutral | N | 0.496135765 | None | None | N |
| I/P | 0.8029 | likely_pathogenic | 0.7113 | pathogenic | -1.189 | Destabilizing | 0.984 | D | 0.461 | neutral | None | None | None | None | N |
| I/Q | 0.4101 | ambiguous | 0.3439 | ambiguous | -1.302 | Destabilizing | 0.953 | D | 0.453 | neutral | None | None | None | None | N |
| I/R | 0.2765 | likely_benign | 0.2097 | benign | -0.613 | Destabilizing | 0.953 | D | 0.464 | neutral | None | None | None | None | N |
| I/S | 0.2811 | likely_benign | 0.2344 | benign | -1.738 | Destabilizing | 0.684 | D | 0.395 | neutral | N | 0.472524555 | None | None | N |
| I/T | 0.1008 | likely_benign | 0.0839 | benign | -1.604 | Destabilizing | 0.684 | D | 0.361 | neutral | N | 0.515134639 | None | None | N |
| I/V | 0.0644 | likely_benign | 0.062 | benign | -1.189 | Destabilizing | 0.001 | N | 0.069 | neutral | N | 0.383972734 | None | None | N |
| I/W | 0.7828 | likely_pathogenic | 0.7332 | pathogenic | -1.507 | Destabilizing | 0.996 | D | 0.577 | neutral | None | None | None | None | N |
| I/Y | 0.5819 | likely_pathogenic | 0.5208 | ambiguous | -1.222 | Destabilizing | 0.953 | D | 0.367 | 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.