Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19136 | 57631;57632;57633 | chr2:178597676;178597675;178597674 | chr2:179462403;179462402;179462401 |
| N2AB | 17495 | 52708;52709;52710 | chr2:178597676;178597675;178597674 | chr2:179462403;179462402;179462401 |
| N2A | 16568 | 49927;49928;49929 | chr2:178597676;178597675;178597674 | chr2:179462403;179462402;179462401 |
| N2B | 10071 | 30436;30437;30438 | chr2:178597676;178597675;178597674 | chr2:179462403;179462402;179462401 |
| Novex-1 | 10196 | 30811;30812;30813 | chr2:178597676;178597675;178597674 | chr2:179462403;179462402;179462401 |
| Novex-2 | 10263 | 31012;31013;31014 | chr2:178597676;178597675;178597674 | chr2:179462403;179462402;179462401 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs553505206  |
-0.108 | 0.999 | N | 0.522 | 0.126 | 0.167679373172 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94175E-04 | None | 0 | 0 | 0 | 0 | 0 |
| E/D | rs553505206 |
-0.108 | 0.999 | N | 0.522 | 0.126 | 0.167679373172 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| E/D | rs553505206 |
-0.108 | 0.999 | N | 0.522 | 0.126 | 0.167679373172 | gnomAD-4.0.0 | 3.8448E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.43285E-05 | None | 0 | 0 | 0 | 1.34016E-05 | 2.84382E-05 |
| E/G | None | None | 1.0 | N | 0.648 | 0.374 | 0.28058544554 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.1609 | likely_benign | 0.2129 | benign | -0.382 | Destabilizing | 0.999 | D | 0.668 | neutral | N | 0.496438943 | None | None | N |
| E/C | 0.8724 | likely_pathogenic | 0.9037 | pathogenic | -0.166 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| E/D | 0.1489 | likely_benign | 0.2003 | benign | -0.508 | Destabilizing | 0.999 | D | 0.522 | neutral | N | 0.448220922 | None | None | N |
| E/F | 0.8455 | likely_pathogenic | 0.8962 | pathogenic | -0.088 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| E/G | 0.2099 | likely_benign | 0.3028 | benign | -0.64 | Destabilizing | 1.0 | D | 0.648 | neutral | N | 0.484872368 | None | None | N |
| E/H | 0.6036 | likely_pathogenic | 0.6864 | pathogenic | 0.021 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| E/I | 0.4679 | ambiguous | 0.5372 | ambiguous | 0.281 | Stabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| E/K | 0.3264 | likely_benign | 0.4396 | ambiguous | 0.043 | Stabilizing | 0.999 | D | 0.647 | neutral | N | 0.450127864 | None | None | N |
| E/L | 0.5971 | likely_pathogenic | 0.7006 | pathogenic | 0.281 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| E/M | 0.559 | ambiguous | 0.6632 | pathogenic | 0.348 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| E/N | 0.3076 | likely_benign | 0.3979 | ambiguous | -0.296 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| E/P | 0.7051 | likely_pathogenic | 0.7451 | pathogenic | 0.082 | Stabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| E/Q | 0.2292 | likely_benign | 0.282 | benign | -0.207 | Destabilizing | 1.0 | D | 0.65 | neutral | N | 0.500287325 | None | None | N |
| E/R | 0.5347 | ambiguous | 0.643 | pathogenic | 0.324 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| E/S | 0.2716 | likely_benign | 0.3379 | benign | -0.492 | Destabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| E/T | 0.2606 | likely_benign | 0.3196 | benign | -0.283 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| E/V | 0.2968 | likely_benign | 0.3803 | ambiguous | 0.082 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | N | 0.504674424 | None | None | N |
| E/W | 0.9387 | likely_pathogenic | 0.9599 | pathogenic | 0.081 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| E/Y | 0.7137 | likely_pathogenic | 0.787 | pathogenic | 0.153 | Stabilizing | 1.0 | D | 0.667 | 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.