Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27684 | 83275;83276;83277 | chr2:178563082;178563081;178563080 | chr2:179427809;179427808;179427807 |
| N2AB | 26043 | 78352;78353;78354 | chr2:178563082;178563081;178563080 | chr2:179427809;179427808;179427807 |
| N2A | 25116 | 75571;75572;75573 | chr2:178563082;178563081;178563080 | chr2:179427809;179427808;179427807 |
| N2B | 18619 | 56080;56081;56082 | chr2:178563082;178563081;178563080 | chr2:179427809;179427808;179427807 |
| Novex-1 | 18744 | 56455;56456;56457 | chr2:178563082;178563081;178563080 | chr2:179427809;179427808;179427807 |
| Novex-2 | 18811 | 56656;56657;56658 | chr2:178563082;178563081;178563080 | chr2:179427809;179427808;179427807 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | None | None | 0.684 | N | 0.489 | 0.278 | 0.766809873248 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-06 | 0 | 0 |
| V/L | rs779966248  |
-0.272 | 0.003 | N | 0.091 | 0.052 | 0.558342666981 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.25 | likely_benign | 0.2423 | benign | -0.87 | Destabilizing | 0.309 | N | 0.315 | neutral | N | 0.457097561 | None | None | I |
| V/C | 0.8293 | likely_pathogenic | 0.8066 | pathogenic | -0.791 | Destabilizing | 0.02 | N | 0.266 | neutral | None | None | None | None | I |
| V/D | 0.786 | likely_pathogenic | 0.7837 | pathogenic | -0.264 | Destabilizing | 0.91 | D | 0.494 | neutral | None | None | None | None | I |
| V/E | 0.7154 | likely_pathogenic | 0.6882 | pathogenic | -0.336 | Destabilizing | 0.884 | D | 0.481 | neutral | N | 0.486380318 | None | None | I |
| V/F | 0.3513 | ambiguous | 0.3617 | ambiguous | -0.81 | Destabilizing | 0.91 | D | 0.452 | neutral | None | None | None | None | I |
| V/G | 0.3294 | likely_benign | 0.3318 | benign | -1.077 | Destabilizing | 0.684 | D | 0.489 | neutral | N | 0.439378592 | None | None | I |
| V/H | 0.854 | likely_pathogenic | 0.8391 | pathogenic | -0.593 | Destabilizing | 0.996 | D | 0.441 | neutral | None | None | None | None | I |
| V/I | 0.0885 | likely_benign | 0.0858 | benign | -0.449 | Destabilizing | 0.037 | N | 0.183 | neutral | None | None | None | None | I |
| V/K | 0.8437 | likely_pathogenic | 0.8198 | pathogenic | -0.708 | Destabilizing | 0.742 | D | 0.49 | neutral | None | None | None | None | I |
| V/L | 0.3165 | likely_benign | 0.3003 | benign | -0.449 | Destabilizing | 0.003 | N | 0.091 | neutral | N | 0.508507816 | None | None | I |
| V/M | 0.1864 | likely_benign | 0.1811 | benign | -0.452 | Destabilizing | 0.078 | N | 0.19 | neutral | N | 0.508854533 | None | None | I |
| V/N | 0.427 | ambiguous | 0.4318 | ambiguous | -0.452 | Destabilizing | 0.91 | D | 0.476 | neutral | None | None | None | None | I |
| V/P | 0.777 | likely_pathogenic | 0.7706 | pathogenic | -0.553 | Destabilizing | 0.953 | D | 0.464 | neutral | None | None | None | None | I |
| V/Q | 0.6724 | likely_pathogenic | 0.6438 | pathogenic | -0.653 | Destabilizing | 0.953 | D | 0.457 | neutral | None | None | None | None | I |
| V/R | 0.8233 | likely_pathogenic | 0.8008 | pathogenic | -0.222 | Destabilizing | 0.953 | D | 0.477 | neutral | None | None | None | None | I |
| V/S | 0.3413 | ambiguous | 0.3337 | benign | -0.936 | Destabilizing | 0.59 | D | 0.413 | neutral | None | None | None | None | I |
| V/T | 0.1671 | likely_benign | 0.1793 | benign | -0.899 | Destabilizing | 0.037 | N | 0.229 | neutral | None | None | None | None | I |
| V/W | 0.9347 | likely_pathogenic | 0.9288 | pathogenic | -0.89 | Destabilizing | 0.996 | D | 0.463 | neutral | None | None | None | None | I |
| V/Y | 0.7577 | likely_pathogenic | 0.7356 | pathogenic | -0.608 | Destabilizing | 0.953 | D | 0.419 | 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.