Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26271 | 79036;79037;79038 | chr2:178567321;178567320;178567319 | chr2:179432048;179432047;179432046 |
| N2AB | 24630 | 74113;74114;74115 | chr2:178567321;178567320;178567319 | chr2:179432048;179432047;179432046 |
| N2A | 23703 | 71332;71333;71334 | chr2:178567321;178567320;178567319 | chr2:179432048;179432047;179432046 |
| N2B | 17206 | 51841;51842;51843 | chr2:178567321;178567320;178567319 | chr2:179432048;179432047;179432046 |
| Novex-1 | 17331 | 52216;52217;52218 | chr2:178567321;178567320;178567319 | chr2:179432048;179432047;179432046 |
| Novex-2 | 17398 | 52417;52418;52419 | chr2:178567321;178567320;178567319 | chr2:179432048;179432047;179432046 |
| 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/I | rs748841355  |
-0.104 | 0.773 | N | 0.395 | 0.121 | 0.493561785454 | gnomAD-2.1.1 | 8.34E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.13E-06 | 1.74155E-04 |
| V/I | rs748841355 |
-0.104 | 0.773 | N | 0.395 | 0.121 | 0.493561785454 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs748841355 |
-0.104 | 0.773 | N | 0.395 | 0.121 | 0.493561785454 | gnomAD-4.0.0 | 5.17895E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 4.53721E-04 | 4.81851E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3148 | likely_benign | 0.29 | benign | -0.323 | Destabilizing | 0.025 | N | 0.279 | neutral | N | 0.475971323 | None | None | I |
| V/C | 0.9028 | likely_pathogenic | 0.8817 | pathogenic | -0.781 | Destabilizing | 0.997 | D | 0.501 | neutral | None | None | None | None | I |
| V/D | 0.7296 | likely_pathogenic | 0.6876 | pathogenic | -0.273 | Destabilizing | 0.983 | D | 0.595 | neutral | N | 0.472893733 | None | None | I |
| V/E | 0.6809 | likely_pathogenic | 0.6307 | pathogenic | -0.392 | Destabilizing | 0.975 | D | 0.503 | neutral | None | None | None | None | I |
| V/F | 0.4278 | ambiguous | 0.3756 | ambiguous | -0.725 | Destabilizing | 0.983 | D | 0.488 | neutral | N | 0.493112296 | None | None | I |
| V/G | 0.5272 | ambiguous | 0.4837 | ambiguous | -0.376 | Destabilizing | 0.935 | D | 0.493 | neutral | N | 0.516529867 | None | None | I |
| V/H | 0.8557 | likely_pathogenic | 0.8324 | pathogenic | -0.036 | Destabilizing | 0.999 | D | 0.626 | neutral | None | None | None | None | I |
| V/I | 0.1036 | likely_benign | 0.0963 | benign | -0.325 | Destabilizing | 0.773 | D | 0.395 | neutral | N | 0.487420468 | None | None | I |
| V/K | 0.739 | likely_pathogenic | 0.7044 | pathogenic | -0.342 | Destabilizing | 0.975 | D | 0.505 | neutral | None | None | None | None | I |
| V/L | 0.4485 | ambiguous | 0.3977 | ambiguous | -0.325 | Destabilizing | 0.63 | D | 0.403 | neutral | N | 0.498117464 | None | None | I |
| V/M | 0.3437 | ambiguous | 0.2985 | benign | -0.524 | Destabilizing | 0.996 | D | 0.502 | neutral | None | None | None | None | I |
| V/N | 0.6194 | likely_pathogenic | 0.5842 | pathogenic | -0.148 | Destabilizing | 0.987 | D | 0.613 | neutral | None | None | None | None | I |
| V/P | 0.5911 | likely_pathogenic | 0.5449 | ambiguous | -0.297 | Destabilizing | 0.987 | D | 0.529 | neutral | None | None | None | None | I |
| V/Q | 0.6842 | likely_pathogenic | 0.6479 | pathogenic | -0.353 | Destabilizing | 0.987 | D | 0.55 | neutral | None | None | None | None | I |
| V/R | 0.6642 | likely_pathogenic | 0.6197 | pathogenic | 0.08 | Stabilizing | 0.987 | D | 0.615 | neutral | None | None | None | None | I |
| V/S | 0.4563 | ambiguous | 0.4241 | ambiguous | -0.459 | Destabilizing | 0.95 | D | 0.416 | neutral | None | None | None | None | I |
| V/T | 0.3524 | ambiguous | 0.3269 | benign | -0.485 | Destabilizing | 0.916 | D | 0.435 | neutral | None | None | None | None | I |
| V/W | 0.9643 | likely_pathogenic | 0.9481 | pathogenic | -0.786 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | I |
| V/Y | 0.8382 | likely_pathogenic | 0.8032 | pathogenic | -0.507 | Destabilizing | 0.996 | D | 0.487 | 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.