Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33656 | 101191;101192;101193 | chr2:178535649;178535648;178535647 | chr2:179400376;179400375;179400374 |
| N2AB | 32015 | 96268;96269;96270 | chr2:178535649;178535648;178535647 | chr2:179400376;179400375;179400374 |
| N2A | 31088 | 93487;93488;93489 | chr2:178535649;178535648;178535647 | chr2:179400376;179400375;179400374 |
| N2B | 24591 | 73996;73997;73998 | chr2:178535649;178535648;178535647 | chr2:179400376;179400375;179400374 |
| Novex-1 | 24716 | 74371;74372;74373 | chr2:178535649;178535648;178535647 | chr2:179400376;179400375;179400374 |
| Novex-2 | 24783 | 74572;74573;74574 | chr2:178535649;178535648;178535647 | chr2:179400376;179400375;179400374 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs559295181  |
-1.147 | None | N | 0.119 | 0.157 | 0.193865811164 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| P/A | rs559295181 |
-1.147 | None | N | 0.119 | 0.157 | 0.193865811164 | gnomAD-4.0.0 | 6.84223E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51902E-05 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs559295181 |
-1.084 | None | N | 0.118 | 0.148 | 0.171388866994 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.56E-05 | 1.65782E-04 |
| P/S | rs559295181 |
-1.084 | None | N | 0.118 | 0.148 | 0.171388866994 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs559295181 |
-1.084 | None | N | 0.118 | 0.148 | 0.171388866994 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| P/S | rs559295181 |
-1.084 | None | N | 0.118 | 0.148 | 0.171388866994 | gnomAD-4.0.0 | 8.05591E-06 | None | None | None | None | N | None | 0 | 3.33289E-05 | None | 0 | 0 | None | 0 | 0 | 9.32374E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2128 | likely_benign | 0.1395 | benign | -1.042 | Destabilizing | None | N | 0.119 | neutral | N | 0.484398806 | None | None | N |
| P/C | 0.7533 | likely_pathogenic | 0.6284 | pathogenic | -0.744 | Destabilizing | 0.223 | N | 0.499 | neutral | None | None | None | None | N |
| P/D | 0.8741 | likely_pathogenic | 0.6924 | pathogenic | -0.686 | Destabilizing | 0.002 | N | 0.404 | neutral | None | None | None | None | N |
| P/E | 0.6666 | likely_pathogenic | 0.4428 | ambiguous | -0.767 | Destabilizing | 0.003 | N | 0.417 | neutral | None | None | None | None | N |
| P/F | 0.8359 | likely_pathogenic | 0.6792 | pathogenic | -1.017 | Destabilizing | 0.469 | N | 0.533 | neutral | None | None | None | None | N |
| P/G | 0.6021 | likely_pathogenic | 0.4212 | ambiguous | -1.259 | Destabilizing | 0.021 | N | 0.409 | neutral | None | None | None | None | N |
| P/H | 0.5563 | ambiguous | 0.3498 | ambiguous | -0.766 | Destabilizing | 0.503 | D | 0.477 | neutral | N | 0.489479338 | None | None | N |
| P/I | 0.4829 | ambiguous | 0.3993 | ambiguous | -0.591 | Destabilizing | 0.201 | N | 0.471 | neutral | None | None | None | None | N |
| P/K | 0.7015 | likely_pathogenic | 0.4515 | ambiguous | -0.812 | Destabilizing | 0.094 | N | 0.389 | neutral | None | None | None | None | N |
| P/L | 0.2839 | likely_benign | 0.1898 | benign | -0.591 | Destabilizing | 0.001 | N | 0.214 | neutral | N | 0.457982995 | None | None | N |
| P/M | 0.5702 | likely_pathogenic | 0.436 | ambiguous | -0.421 | Destabilizing | 0.249 | N | 0.472 | neutral | None | None | None | None | N |
| P/N | 0.6596 | likely_pathogenic | 0.4513 | ambiguous | -0.486 | Destabilizing | 0.03 | N | 0.434 | neutral | None | None | None | None | N |
| P/Q | 0.386 | ambiguous | 0.2385 | benign | -0.753 | Destabilizing | 0.003 | N | 0.128 | neutral | None | None | None | None | N |
| P/R | 0.5428 | ambiguous | 0.3353 | benign | -0.238 | Destabilizing | 0.275 | N | 0.455 | neutral | N | 0.452171744 | None | None | N |
| P/S | 0.3212 | likely_benign | 0.198 | benign | -0.949 | Destabilizing | None | N | 0.118 | neutral | N | 0.453555824 | None | None | N |
| P/T | 0.2387 | likely_benign | 0.1623 | benign | -0.928 | Destabilizing | None | N | 0.131 | neutral | N | 0.464100891 | None | None | N |
| P/V | 0.3391 | likely_benign | 0.3034 | benign | -0.706 | Destabilizing | 0.018 | N | 0.396 | neutral | None | None | None | None | N |
| P/W | 0.9107 | likely_pathogenic | 0.818 | pathogenic | -1.083 | Destabilizing | 0.976 | D | 0.485 | neutral | None | None | None | None | N |
| P/Y | 0.8423 | likely_pathogenic | 0.6591 | pathogenic | -0.812 | Destabilizing | 0.782 | D | 0.54 | 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.