Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19571 | 58936;58937;58938 | chr2:178593589;178593588;178593587 | chr2:179458316;179458315;179458314 |
| N2AB | 17930 | 54013;54014;54015 | chr2:178593589;178593588;178593587 | chr2:179458316;179458315;179458314 |
| N2A | 17003 | 51232;51233;51234 | chr2:178593589;178593588;178593587 | chr2:179458316;179458315;179458314 |
| N2B | 10506 | 31741;31742;31743 | chr2:178593589;178593588;178593587 | chr2:179458316;179458315;179458314 |
| Novex-1 | 10631 | 32116;32117;32118 | chr2:178593589;178593588;178593587 | chr2:179458316;179458315;179458314 |
| Novex-2 | 10698 | 32317;32318;32319 | chr2:178593589;178593588;178593587 | chr2:179458316;179458315;179458314 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/V | rs770228515  |
-1.461 | None | N | 0.149 | 0.276 | 0.357519025918 | gnomAD-2.1.1 | 8.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| M/V | rs770228515 |
-1.461 | None | N | 0.149 | 0.276 | 0.357519025918 | gnomAD-4.0.0 | 8.90388E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.07974E-05 | 0 | 1.65893E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.3355 | likely_benign | 0.3268 | benign | -1.945 | Destabilizing | 0.029 | N | 0.229 | neutral | None | None | None | None | N |
| M/C | 0.5262 | ambiguous | 0.5366 | ambiguous | -1.315 | Destabilizing | 0.878 | D | 0.412 | neutral | None | None | None | None | N |
| M/D | 0.9056 | likely_pathogenic | 0.8974 | pathogenic | -0.552 | Destabilizing | 0.403 | N | 0.555 | neutral | None | None | None | None | N |
| M/E | 0.4462 | ambiguous | 0.4249 | ambiguous | -0.479 | Destabilizing | 0.403 | N | 0.458 | neutral | None | None | None | None | N |
| M/F | 0.354 | ambiguous | 0.342 | ambiguous | -0.827 | Destabilizing | 0.25 | N | 0.297 | neutral | None | None | None | None | N |
| M/G | 0.6752 | likely_pathogenic | 0.6517 | pathogenic | -2.286 | Highly Destabilizing | 0.403 | N | 0.425 | neutral | None | None | None | None | N |
| M/H | 0.5574 | ambiguous | 0.5405 | ambiguous | -1.16 | Destabilizing | 0.878 | D | 0.577 | neutral | None | None | None | None | N |
| M/I | 0.2555 | likely_benign | 0.2569 | benign | -1.037 | Destabilizing | None | N | 0.239 | neutral | N | 0.460628151 | None | None | N |
| M/K | 0.156 | likely_benign | 0.1486 | benign | -0.666 | Destabilizing | 0.201 | N | 0.38 | neutral | N | 0.488281686 | None | None | N |
| M/L | 0.1555 | likely_benign | 0.1419 | benign | -1.037 | Destabilizing | 0.01 | N | 0.146 | neutral | N | 0.467442267 | None | None | N |
| M/N | 0.67 | likely_pathogenic | 0.6538 | pathogenic | -0.635 | Destabilizing | 0.403 | N | 0.565 | neutral | None | None | None | None | N |
| M/P | 0.9512 | likely_pathogenic | 0.9371 | pathogenic | -1.315 | Destabilizing | 0.672 | D | 0.563 | neutral | None | None | None | None | N |
| M/Q | 0.1915 | likely_benign | 0.1895 | benign | -0.635 | Destabilizing | 0.672 | D | 0.359 | neutral | None | None | None | None | N |
| M/R | 0.1895 | likely_benign | 0.1834 | benign | -0.219 | Destabilizing | 0.337 | N | 0.473 | neutral | N | 0.517737801 | None | None | N |
| M/S | 0.4647 | ambiguous | 0.4585 | ambiguous | -1.28 | Destabilizing | 0.064 | N | 0.262 | neutral | None | None | None | None | N |
| M/T | 0.1814 | likely_benign | 0.1845 | benign | -1.081 | Destabilizing | None | N | 0.221 | neutral | N | 0.434465844 | None | None | N |
| M/V | 0.0625 | likely_benign | 0.0641 | benign | -1.315 | Destabilizing | None | N | 0.149 | neutral | N | 0.399542407 | None | None | N |
| M/W | 0.7131 | likely_pathogenic | 0.686 | pathogenic | -0.732 | Destabilizing | 0.964 | D | 0.412 | neutral | None | None | None | None | N |
| M/Y | 0.6312 | likely_pathogenic | 0.6131 | pathogenic | -0.793 | Destabilizing | 0.703 | D | 0.513 | 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.