Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13716 | 41371;41372;41373 | chr2:178636581;178636580;178636579 | chr2:179501308;179501307;179501306 |
| N2AB | 12075 | 36448;36449;36450 | chr2:178636581;178636580;178636579 | chr2:179501308;179501307;179501306 |
| N2A | 11148 | 33667;33668;33669 | chr2:178636581;178636580;178636579 | chr2:179501308;179501307;179501306 |
| N2B | 4651 | 14176;14177;14178 | chr2:178636581;178636580;178636579 | chr2:179501308;179501307;179501306 |
| Novex-1 | 4776 | 14551;14552;14553 | chr2:178636581;178636580;178636579 | chr2:179501308;179501307;179501306 |
| Novex-2 | 4843 | 14752;14753;14754 | chr2:178636581;178636580;178636579 | chr2:179501308;179501307;179501306 |
| 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 | None | None | 0.201 | N | 0.643 | 0.306 | 0.59589940523 | gnomAD-4.0.0 | 3.18385E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86566E-05 | 0 |
| I/V | rs531807386  |
-0.124 | 0.001 | N | 0.257 | 0.06 | 0.396044805602 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 4.64E-05 | 0 | 0 |
| I/V | rs531807386 |
-0.124 | 0.001 | N | 0.257 | 0.06 | 0.396044805602 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93874E-04 | None | 0 | 0 | 0 | 2.07297E-04 | 0 |
| I/V | rs531807386 |
-0.124 | 0.001 | N | 0.257 | 0.06 | 0.396044805602 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| I/V | rs531807386 |
-0.124 | 0.001 | N | 0.257 | 0.06 | 0.396044805602 | gnomAD-4.0.0 | 4.95829E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.46728E-05 | None | 1.56216E-05 | 0 | 3.39101E-06 | 1.09803E-05 | 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 | 0.5484 | ambiguous | 0.7346 | pathogenic | -0.67 | Destabilizing | 0.25 | N | 0.623 | neutral | None | None | None | None | N |
| I/C | 0.9181 | likely_pathogenic | 0.9504 | pathogenic | -0.594 | Destabilizing | 0.947 | D | 0.679 | prob.neutral | None | None | None | None | N |
| I/D | 0.9293 | likely_pathogenic | 0.9633 | pathogenic | -0.094 | Destabilizing | 0.826 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/E | 0.8284 | likely_pathogenic | 0.9071 | pathogenic | -0.18 | Destabilizing | 0.826 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/F | 0.3315 | likely_benign | 0.4941 | ambiguous | -0.625 | Destabilizing | 0.638 | D | 0.62 | neutral | N | 0.502574004 | None | None | N |
| I/G | 0.8588 | likely_pathogenic | 0.9309 | pathogenic | -0.851 | Destabilizing | 0.826 | D | 0.724 | prob.delet. | None | None | None | None | N |
| I/H | 0.8272 | likely_pathogenic | 0.9068 | pathogenic | -0.143 | Destabilizing | 0.982 | D | 0.709 | prob.delet. | None | None | None | None | N |
| I/K | 0.7558 | likely_pathogenic | 0.8484 | pathogenic | -0.345 | Destabilizing | 0.826 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/L | 0.1622 | likely_benign | 0.2753 | benign | -0.311 | Destabilizing | 0.043 | N | 0.403 | neutral | N | 0.482950403 | None | None | N |
| I/M | 0.1418 | likely_benign | 0.2278 | benign | -0.343 | Destabilizing | 0.638 | D | 0.623 | neutral | N | 0.508330543 | None | None | N |
| I/N | 0.5677 | likely_pathogenic | 0.7042 | pathogenic | -0.122 | Destabilizing | 0.916 | D | 0.727 | prob.delet. | N | 0.466499773 | None | None | N |
| I/P | 0.9421 | likely_pathogenic | 0.9536 | pathogenic | -0.397 | Destabilizing | 0.935 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/Q | 0.7046 | likely_pathogenic | 0.8292 | pathogenic | -0.343 | Destabilizing | 0.935 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/R | 0.7212 | likely_pathogenic | 0.8318 | pathogenic | 0.196 | Stabilizing | 0.826 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/S | 0.5637 | ambiguous | 0.7149 | pathogenic | -0.61 | Destabilizing | 0.638 | D | 0.682 | prob.neutral | N | 0.453872901 | None | None | N |
| I/T | 0.4529 | ambiguous | 0.598 | pathogenic | -0.584 | Destabilizing | 0.201 | N | 0.643 | neutral | N | 0.414817738 | None | None | N |
| I/V | 0.0686 | likely_benign | 0.0749 | benign | -0.397 | Destabilizing | 0.001 | N | 0.257 | neutral | N | 0.434072639 | None | None | N |
| I/W | 0.9534 | likely_pathogenic | 0.9687 | pathogenic | -0.639 | Destabilizing | 0.982 | D | 0.687 | prob.neutral | None | None | None | None | N |
| I/Y | 0.7876 | likely_pathogenic | 0.8754 | pathogenic | -0.388 | Destabilizing | 0.826 | D | 0.708 | prob.delet. | 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.