Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19142 | 57649;57650;57651 | chr2:178597658;178597657;178597656 | chr2:179462385;179462384;179462383 |
| N2AB | 17501 | 52726;52727;52728 | chr2:178597658;178597657;178597656 | chr2:179462385;179462384;179462383 |
| N2A | 16574 | 49945;49946;49947 | chr2:178597658;178597657;178597656 | chr2:179462385;179462384;179462383 |
| N2B | 10077 | 30454;30455;30456 | chr2:178597658;178597657;178597656 | chr2:179462385;179462384;179462383 |
| Novex-1 | 10202 | 30829;30830;30831 | chr2:178597658;178597657;178597656 | chr2:179462385;179462384;179462383 |
| Novex-2 | 10269 | 31030;31031;31032 | chr2:178597658;178597657;178597656 | chr2:179462385;179462384;179462383 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.117 | N | 0.281 | 0.229 | 0.258779203287 | gnomAD-4.0.0 | 1.59268E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86E-06 | 0 | 0 |
| T/I | rs1576218735  |
None | 0.993 | D | 0.613 | 0.433 | 0.731554227051 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94326E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs1576218735 |
None | 0.993 | D | 0.613 | 0.433 | 0.731554227051 | gnomAD-4.0.0 | 2.03011E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.13947E-04 | None | 0 | 0 | 1.20498E-06 | 0 | 0 |
| T/P | rs760195565 |
-0.481 | 0.997 | N | 0.61 | 0.533 | None | gnomAD-4.0.0 | 6.37075E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 7.54888E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.3743 | ambiguous | 0.3325 | benign | -0.306 | Destabilizing | 0.117 | N | 0.281 | neutral | N | 0.518975526 | None | None | N |
| T/C | 0.9333 | likely_pathogenic | 0.9132 | pathogenic | -0.217 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | N |
| T/D | 0.8285 | likely_pathogenic | 0.7903 | pathogenic | 0.106 | Stabilizing | 0.998 | D | 0.61 | neutral | None | None | None | None | N |
| T/E | 0.8879 | likely_pathogenic | 0.8658 | pathogenic | 0.008 | Stabilizing | 0.995 | D | 0.561 | neutral | None | None | None | None | N |
| T/F | 0.9118 | likely_pathogenic | 0.8967 | pathogenic | -0.998 | Destabilizing | 0.999 | D | 0.684 | prob.neutral | None | None | None | None | N |
| T/G | 0.6172 | likely_pathogenic | 0.5334 | ambiguous | -0.358 | Destabilizing | 0.966 | D | 0.533 | neutral | None | None | None | None | N |
| T/H | 0.8251 | likely_pathogenic | 0.7777 | pathogenic | -0.706 | Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| T/I | 0.9024 | likely_pathogenic | 0.8859 | pathogenic | -0.29 | Destabilizing | 0.993 | D | 0.613 | neutral | D | 0.527269722 | None | None | N |
| T/K | 0.7962 | likely_pathogenic | 0.7626 | pathogenic | -0.223 | Destabilizing | 0.993 | D | 0.559 | neutral | D | 0.52665086 | None | None | N |
| T/L | 0.5399 | ambiguous | 0.5033 | ambiguous | -0.29 | Destabilizing | 0.983 | D | 0.493 | neutral | None | None | None | None | N |
| T/M | 0.3955 | ambiguous | 0.3635 | ambiguous | -0.061 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | N |
| T/N | 0.4631 | ambiguous | 0.3752 | ambiguous | -0.015 | Destabilizing | 0.998 | D | 0.579 | neutral | None | None | None | None | N |
| T/P | 0.7912 | likely_pathogenic | 0.7503 | pathogenic | -0.272 | Destabilizing | 0.997 | D | 0.61 | neutral | N | 0.490153463 | None | None | N |
| T/Q | 0.8012 | likely_pathogenic | 0.7411 | pathogenic | -0.247 | Destabilizing | 0.998 | D | 0.63 | neutral | None | None | None | None | N |
| T/R | 0.7933 | likely_pathogenic | 0.7527 | pathogenic | -0.018 | Destabilizing | 0.997 | D | 0.594 | neutral | D | 0.532443469 | None | None | N |
| T/S | 0.3227 | likely_benign | 0.26 | benign | -0.176 | Destabilizing | 0.955 | D | 0.379 | neutral | N | 0.517108657 | None | None | N |
| T/V | 0.7228 | likely_pathogenic | 0.6944 | pathogenic | -0.272 | Destabilizing | 0.966 | D | 0.423 | neutral | None | None | None | None | N |
| T/W | 0.9796 | likely_pathogenic | 0.9756 | pathogenic | -1.05 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| T/Y | 0.9376 | likely_pathogenic | 0.9206 | pathogenic | -0.741 | Destabilizing | 0.999 | D | 0.672 | 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.