Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24616 | 74071;74072;74073 | chr2:178572286;178572285;178572284 | chr2:179437013;179437012;179437011 |
| N2AB | 22975 | 69148;69149;69150 | chr2:178572286;178572285;178572284 | chr2:179437013;179437012;179437011 |
| N2A | 22048 | 66367;66368;66369 | chr2:178572286;178572285;178572284 | chr2:179437013;179437012;179437011 |
| N2B | 15551 | 46876;46877;46878 | chr2:178572286;178572285;178572284 | chr2:179437013;179437012;179437011 |
| Novex-1 | 15676 | 47251;47252;47253 | chr2:178572286;178572285;178572284 | chr2:179437013;179437012;179437011 |
| Novex-2 | 15743 | 47452;47453;47454 | chr2:178572286;178572285;178572284 | chr2:179437013;179437012;179437011 |
| 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/Q | rs201694149  |
-0.618 | 0.999 | N | 0.611 | 0.262 | None | gnomAD-2.1.1 | 9.31E-05 | None | None | None | None | N | None | 1.65412E-04 | 3.9696E-04 | None | 0 | 1.03316E-04 | None | 0 | None | 0 | 3.14E-05 | 2.81849E-04 |
| R/Q | rs201694149 |
-0.618 | 0.999 | N | 0.611 | 0.262 | None | gnomAD-3.1.2 | 6.58E-05 | None | None | None | None | N | None | 1.20703E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 9.56023E-04 |
| R/Q | rs201694149 |
-0.618 | 0.999 | N | 0.611 | 0.262 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| R/Q | rs201694149 |
-0.618 | 0.999 | N | 0.611 | 0.262 | None | gnomAD-4.0.0 | 3.28692E-05 | None | None | None | None | N | None | 8.00256E-05 | 3.6685E-04 | None | 0 | 8.94654E-05 | None | 0 | 0 | 1.35725E-05 | 0 | 8.00974E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3514 | ambiguous | 0.3582 | ambiguous | -0.407 | Destabilizing | 0.988 | D | 0.543 | neutral | None | None | None | None | N |
| R/C | 0.1622 | likely_benign | 0.1644 | benign | -0.428 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| R/D | 0.8351 | likely_pathogenic | 0.8307 | pathogenic | -0.009 | Destabilizing | 0.998 | D | 0.633 | neutral | None | None | None | None | N |
| R/E | 0.4537 | ambiguous | 0.4523 | ambiguous | 0.065 | Stabilizing | 0.961 | D | 0.505 | neutral | None | None | None | None | N |
| R/F | 0.6609 | likely_pathogenic | 0.6228 | pathogenic | -0.566 | Destabilizing | 0.999 | D | 0.817 | deleterious | None | None | None | None | N |
| R/G | 0.3945 | ambiguous | 0.3762 | ambiguous | -0.633 | Destabilizing | 0.997 | D | 0.551 | neutral | N | 0.479669697 | None | None | N |
| R/H | 0.1609 | likely_benign | 0.147 | benign | -1.018 | Destabilizing | 0.999 | D | 0.621 | neutral | None | None | None | None | N |
| R/I | 0.194 | likely_benign | 0.1882 | benign | 0.164 | Stabilizing | 0.999 | D | 0.85 | deleterious | None | None | None | None | N |
| R/K | 0.08 | likely_benign | 0.0792 | benign | -0.4 | Destabilizing | 0.053 | N | 0.132 | neutral | None | None | None | None | N |
| R/L | 0.2546 | likely_benign | 0.2352 | benign | 0.164 | Stabilizing | 0.993 | D | 0.551 | neutral | N | 0.435436131 | None | None | N |
| R/M | 0.2526 | likely_benign | 0.2481 | benign | -0.114 | Destabilizing | 1.0 | D | 0.61 | neutral | None | None | None | None | N |
| R/N | 0.6827 | likely_pathogenic | 0.6671 | pathogenic | 0.032 | Stabilizing | 0.998 | D | 0.565 | neutral | None | None | None | None | N |
| R/P | 0.2516 | likely_benign | 0.2629 | benign | -0.006 | Destabilizing | 1.0 | D | 0.863 | deleterious | N | 0.343776763 | None | None | N |
| R/Q | 0.1152 | likely_benign | 0.1118 | benign | -0.174 | Destabilizing | 0.999 | D | 0.611 | neutral | N | 0.447693352 | None | None | N |
| R/S | 0.5538 | ambiguous | 0.5441 | ambiguous | -0.566 | Destabilizing | 0.988 | D | 0.646 | neutral | None | None | None | None | N |
| R/T | 0.261 | likely_benign | 0.2507 | benign | -0.342 | Destabilizing | 0.994 | D | 0.587 | neutral | None | None | None | None | N |
| R/V | 0.2435 | likely_benign | 0.2433 | benign | -0.006 | Destabilizing | 0.994 | D | 0.781 | deleterious | None | None | None | None | N |
| R/W | 0.3621 | ambiguous | 0.3207 | benign | -0.434 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| R/Y | 0.5147 | ambiguous | 0.4789 | ambiguous | -0.065 | Destabilizing | 0.999 | D | 0.855 | deleterious | 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.