Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26602 | 80029;80030;80031 | chr2:178566328;178566327;178566326 | chr2:179431055;179431054;179431053 |
| N2AB | 24961 | 75106;75107;75108 | chr2:178566328;178566327;178566326 | chr2:179431055;179431054;179431053 |
| N2A | 24034 | 72325;72326;72327 | chr2:178566328;178566327;178566326 | chr2:179431055;179431054;179431053 |
| N2B | 17537 | 52834;52835;52836 | chr2:178566328;178566327;178566326 | chr2:179431055;179431054;179431053 |
| Novex-1 | 17662 | 53209;53210;53211 | chr2:178566328;178566327;178566326 | chr2:179431055;179431054;179431053 |
| Novex-2 | 17729 | 53410;53411;53412 | chr2:178566328;178566327;178566326 | chr2:179431055;179431054;179431053 |
| 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 | rs1165543503  |
-1.32 | 0.822 | D | 0.541 | 0.471 | 0.780957376407 | gnomAD-2.1.1 | 7.14E-06 | None | None | None | None | I | None | 0 | 5.66E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1165543503 |
-1.32 | 0.822 | D | 0.541 | 0.471 | 0.780957376407 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 1.31337E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1165543503 |
-1.32 | 0.822 | D | 0.541 | 0.471 | 0.780957376407 | gnomAD-4.0.0 | 3.84455E-06 | None | None | None | None | I | None | 0 | 5.08802E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.6906 | likely_pathogenic | 0.6563 | pathogenic | -1.577 | Destabilizing | 0.86 | D | 0.49 | neutral | None | None | None | None | I |
| I/C | 0.8095 | likely_pathogenic | 0.8074 | pathogenic | -1.112 | Destabilizing | 0.998 | D | 0.57 | neutral | None | None | None | None | I |
| I/D | 0.9734 | likely_pathogenic | 0.9627 | pathogenic | -0.899 | Destabilizing | 0.915 | D | 0.648 | neutral | None | None | None | None | I |
| I/E | 0.9305 | likely_pathogenic | 0.9088 | pathogenic | -0.857 | Destabilizing | 0.956 | D | 0.661 | neutral | None | None | None | None | I |
| I/F | 0.2504 | likely_benign | 0.2334 | benign | -0.947 | Destabilizing | 0.99 | D | 0.504 | neutral | N | 0.513827125 | None | None | I |
| I/G | 0.9417 | likely_pathogenic | 0.9316 | pathogenic | -1.939 | Destabilizing | 0.754 | D | 0.63 | neutral | None | None | None | None | I |
| I/H | 0.8457 | likely_pathogenic | 0.8296 | pathogenic | -1.217 | Destabilizing | 0.994 | D | 0.705 | prob.neutral | None | None | None | None | I |
| I/K | 0.8213 | likely_pathogenic | 0.7881 | pathogenic | -1.193 | Destabilizing | 0.956 | D | 0.668 | neutral | None | None | None | None | I |
| I/L | 0.1335 | likely_benign | 0.1332 | benign | -0.643 | Destabilizing | 0.795 | D | 0.404 | neutral | N | 0.441552105 | None | None | I |
| I/M | 0.1315 | likely_benign | 0.1315 | benign | -0.62 | Destabilizing | 0.99 | D | 0.481 | neutral | N | 0.503160712 | None | None | I |
| I/N | 0.7822 | likely_pathogenic | 0.7461 | pathogenic | -1.076 | Destabilizing | 0.014 | N | 0.438 | neutral | D | 0.525943899 | None | None | I |
| I/P | 0.9689 | likely_pathogenic | 0.967 | pathogenic | -0.923 | Destabilizing | 0.993 | D | 0.717 | prob.delet. | None | None | None | None | I |
| I/Q | 0.8264 | likely_pathogenic | 0.8039 | pathogenic | -1.155 | Destabilizing | 0.956 | D | 0.723 | prob.delet. | None | None | None | None | I |
| I/R | 0.7707 | likely_pathogenic | 0.7306 | pathogenic | -0.729 | Destabilizing | 0.956 | D | 0.709 | prob.delet. | None | None | None | None | I |
| I/S | 0.7752 | likely_pathogenic | 0.7427 | pathogenic | -1.725 | Destabilizing | 0.698 | D | 0.565 | neutral | N | 0.502052746 | None | None | I |
| I/T | 0.562 | ambiguous | 0.5131 | ambiguous | -1.555 | Destabilizing | 0.822 | D | 0.541 | neutral | D | 0.534771698 | None | None | I |
| I/V | 0.1064 | likely_benign | 0.099 | benign | -0.923 | Destabilizing | 0.795 | D | 0.449 | neutral | N | 0.43735422 | None | None | I |
| I/W | 0.8482 | likely_pathogenic | 0.8489 | pathogenic | -1.064 | Destabilizing | 0.998 | D | 0.655 | neutral | None | None | None | None | I |
| I/Y | 0.6997 | likely_pathogenic | 0.6908 | pathogenic | -0.827 | Destabilizing | 0.993 | D | 0.611 | 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.