Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27152 | 81679;81680;81681 | chr2:178564678;178564677;178564676 | chr2:179429405;179429404;179429403 |
| N2AB | 25511 | 76756;76757;76758 | chr2:178564678;178564677;178564676 | chr2:179429405;179429404;179429403 |
| N2A | 24584 | 73975;73976;73977 | chr2:178564678;178564677;178564676 | chr2:179429405;179429404;179429403 |
| N2B | 18087 | 54484;54485;54486 | chr2:178564678;178564677;178564676 | chr2:179429405;179429404;179429403 |
| Novex-1 | 18212 | 54859;54860;54861 | chr2:178564678;178564677;178564676 | chr2:179429405;179429404;179429403 |
| Novex-2 | 18279 | 55060;55061;55062 | chr2:178564678;178564677;178564676 | chr2:179429405;179429404;179429403 |
| 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 | rs756551242  |
-0.176 | 0.822 | N | 0.509 | 0.19 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/T | rs756551242 |
-0.176 | 0.822 | N | 0.509 | 0.19 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs756551242 |
-0.176 | 0.822 | N | 0.509 | 0.19 | None | gnomAD-4.0.0 | 4.33879E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93369E-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 | 0.2132 | likely_benign | 0.2137 | benign | -0.58 | Destabilizing | 0.559 | D | 0.478 | neutral | None | None | None | None | I |
| I/C | 0.7033 | likely_pathogenic | 0.7119 | pathogenic | -0.846 | Destabilizing | 0.998 | D | 0.471 | neutral | None | None | None | None | I |
| I/D | 0.8146 | likely_pathogenic | 0.8047 | pathogenic | -0.224 | Destabilizing | 0.993 | D | 0.57 | neutral | None | None | None | None | I |
| I/E | 0.6824 | likely_pathogenic | 0.7026 | pathogenic | -0.31 | Destabilizing | 0.978 | D | 0.573 | neutral | None | None | None | None | I |
| I/F | 0.2592 | likely_benign | 0.2415 | benign | -0.602 | Destabilizing | 0.942 | D | 0.371 | neutral | N | 0.501714718 | None | None | I |
| I/G | 0.6965 | likely_pathogenic | 0.6655 | pathogenic | -0.716 | Destabilizing | 0.978 | D | 0.561 | neutral | None | None | None | None | I |
| I/H | 0.6377 | likely_pathogenic | 0.6108 | pathogenic | 0.035 | Stabilizing | 0.998 | D | 0.563 | neutral | None | None | None | None | I |
| I/K | 0.444 | ambiguous | 0.4633 | ambiguous | -0.408 | Destabilizing | 0.978 | D | 0.565 | neutral | None | None | None | None | I |
| I/L | 0.1223 | likely_benign | 0.1163 | benign | -0.343 | Destabilizing | 0.006 | N | 0.133 | neutral | N | 0.475170742 | None | None | I |
| I/M | 0.0971 | likely_benign | 0.0896 | benign | -0.555 | Destabilizing | 0.294 | N | 0.374 | neutral | N | 0.473189229 | None | None | I |
| I/N | 0.4451 | ambiguous | 0.4284 | ambiguous | -0.33 | Destabilizing | 0.99 | D | 0.567 | neutral | N | 0.470226241 | None | None | I |
| I/P | 0.7608 | likely_pathogenic | 0.6546 | pathogenic | -0.391 | Destabilizing | 0.993 | D | 0.565 | neutral | None | None | None | None | I |
| I/Q | 0.5248 | ambiguous | 0.534 | ambiguous | -0.517 | Destabilizing | 0.978 | D | 0.565 | neutral | None | None | None | None | I |
| I/R | 0.3169 | likely_benign | 0.3319 | benign | 0.124 | Stabilizing | 0.978 | D | 0.566 | neutral | None | None | None | None | I |
| I/S | 0.3081 | likely_benign | 0.295 | benign | -0.751 | Destabilizing | 0.97 | D | 0.502 | neutral | N | 0.470551569 | None | None | I |
| I/T | 0.2087 | likely_benign | 0.1956 | benign | -0.729 | Destabilizing | 0.822 | D | 0.509 | neutral | N | 0.51555314 | None | None | I |
| I/V | 0.084 | likely_benign | 0.0844 | benign | -0.391 | Destabilizing | 0.014 | N | 0.166 | neutral | N | 0.5001624 | None | None | I |
| I/W | 0.8484 | likely_pathogenic | 0.8128 | pathogenic | -0.613 | Destabilizing | 0.998 | D | 0.655 | neutral | None | None | None | None | I |
| I/Y | 0.624 | likely_pathogenic | 0.6198 | pathogenic | -0.381 | Destabilizing | 0.978 | D | 0.462 | 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.