Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32333 | 97222;97223;97224 | chr2:178542857;178542856;178542855 | chr2:179407584;179407583;179407582 |
| N2AB | 30692 | 92299;92300;92301 | chr2:178542857;178542856;178542855 | chr2:179407584;179407583;179407582 |
| N2A | 29765 | 89518;89519;89520 | chr2:178542857;178542856;178542855 | chr2:179407584;179407583;179407582 |
| N2B | 23268 | 70027;70028;70029 | chr2:178542857;178542856;178542855 | chr2:179407584;179407583;179407582 |
| Novex-1 | 23393 | 70402;70403;70404 | chr2:178542857;178542856;178542855 | chr2:179407584;179407583;179407582 |
| Novex-2 | 23460 | 70603;70604;70605 | chr2:178542857;178542856;178542855 | chr2:179407584;179407583;179407582 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs368918455  |
-0.084 | 1.0 | N | 0.671 | 0.412 | None | gnomAD-2.1.1 | 7.17E-06 | None | None | None | None | I | None | 8.28E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/C | rs368918455 |
-0.084 | 1.0 | N | 0.671 | 0.412 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 9.66E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs368918455 |
-0.084 | 1.0 | N | 0.671 | 0.412 | None | gnomAD-4.0.0 | 6.19715E-06 | None | None | None | None | I | None | 5.34074E-05 | 0 | None | 0 | 2.22836E-05 | None | 0 | 0 | 4.23813E-06 | 0 | 0 |
| R/H | rs138846756 |
-0.661 | 1.0 | N | 0.513 | 0.324 | None | gnomAD-2.1.1 | 4.26594E-04 | None | None | None | None | I | None | 3.80763E-03 | 5.65835E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.94E-05 | 1.40687E-04 |
| R/H | rs138846756 |
-0.661 | 1.0 | N | 0.513 | 0.324 | None | gnomAD-3.1.2 | 9.40406E-04 | None | None | None | None | I | None | 3.3095E-03 | 3.27654E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs138846756 |
-0.661 | 1.0 | N | 0.513 | 0.324 | None | 1000 genomes | 1.19808E-03 | None | None | None | None | I | None | 4.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/H | rs138846756 |
-0.661 | 1.0 | N | 0.513 | 0.324 | None | gnomAD-4.0.0 | 2.21846E-04 | None | None | None | None | I | None | 3.25377E-03 | 4.33333E-04 | None | 0 | 0 | None | 0 | 0 | 6.01805E-05 | 2.19616E-05 | 2.40077E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7944 | likely_pathogenic | 0.7387 | pathogenic | 0.129 | Stabilizing | 0.985 | D | 0.57 | neutral | None | None | None | None | I |
| R/C | 0.2451 | likely_benign | 0.2298 | benign | -0.083 | Destabilizing | 1.0 | D | 0.671 | neutral | N | 0.512529556 | None | None | I |
| R/D | 0.9489 | likely_pathogenic | 0.9298 | pathogenic | -0.245 | Destabilizing | 0.998 | D | 0.566 | neutral | None | None | None | None | I |
| R/E | 0.741 | likely_pathogenic | 0.7009 | pathogenic | -0.192 | Destabilizing | 0.985 | D | 0.535 | neutral | None | None | None | None | I |
| R/F | 0.7084 | likely_pathogenic | 0.6504 | pathogenic | -0.14 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | I |
| R/G | 0.74 | likely_pathogenic | 0.6765 | pathogenic | -0.035 | Destabilizing | 0.996 | D | 0.58 | neutral | N | 0.490567855 | None | None | I |
| R/H | 0.1599 | likely_benign | 0.1557 | benign | -0.599 | Destabilizing | 1.0 | D | 0.513 | neutral | N | 0.450403662 | None | None | I |
| R/I | 0.373 | ambiguous | 0.3476 | ambiguous | 0.518 | Stabilizing | 0.999 | D | 0.624 | neutral | None | None | None | None | I |
| R/K | 0.1594 | likely_benign | 0.1612 | benign | -0.017 | Destabilizing | 0.271 | N | 0.292 | neutral | None | None | None | None | I |
| R/L | 0.3951 | ambiguous | 0.3418 | ambiguous | 0.518 | Stabilizing | 0.996 | D | 0.58 | neutral | N | 0.482380008 | None | None | I |
| R/M | 0.4949 | ambiguous | 0.4673 | ambiguous | 0.029 | Stabilizing | 1.0 | D | 0.541 | neutral | None | None | None | None | I |
| R/N | 0.8382 | likely_pathogenic | 0.803 | pathogenic | 0.121 | Stabilizing | 0.998 | D | 0.52 | neutral | None | None | None | None | I |
| R/P | 0.9766 | likely_pathogenic | 0.9658 | pathogenic | 0.408 | Stabilizing | 1.0 | D | 0.605 | neutral | N | 0.490821345 | None | None | I |
| R/Q | 0.1651 | likely_benign | 0.164 | benign | 0.076 | Stabilizing | 0.996 | D | 0.539 | neutral | None | None | None | None | I |
| R/S | 0.7937 | likely_pathogenic | 0.7347 | pathogenic | -0.063 | Destabilizing | 0.992 | D | 0.597 | neutral | N | 0.458270997 | None | None | I |
| R/T | 0.5993 | likely_pathogenic | 0.5442 | ambiguous | 0.105 | Stabilizing | 0.993 | D | 0.546 | neutral | None | None | None | None | I |
| R/V | 0.5309 | ambiguous | 0.4757 | ambiguous | 0.408 | Stabilizing | 0.998 | D | 0.608 | neutral | None | None | None | None | I |
| R/W | 0.3047 | likely_benign | 0.2608 | benign | -0.306 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| R/Y | 0.4982 | ambiguous | 0.4526 | ambiguous | 0.108 | Stabilizing | 0.999 | D | 0.612 | 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.