Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14971 | 45136;45137;45138 | chr2:178622672;178622671;178622670 | chr2:179487399;179487398;179487397 |
| N2AB | 13330 | 40213;40214;40215 | chr2:178622672;178622671;178622670 | chr2:179487399;179487398;179487397 |
| N2A | 12403 | 37432;37433;37434 | chr2:178622672;178622671;178622670 | chr2:179487399;179487398;179487397 |
| N2B | 5906 | 17941;17942;17943 | chr2:178622672;178622671;178622670 | chr2:179487399;179487398;179487397 |
| Novex-1 | 6031 | 18316;18317;18318 | chr2:178622672;178622671;178622670 | chr2:179487399;179487398;179487397 |
| Novex-2 | 6098 | 18517;18518;18519 | chr2:178622672;178622671;178622670 | chr2:179487399;179487398;179487397 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | rs757693661  |
None | 0.999 | N | 0.679 | 0.32 | 0.3571064206 | gnomAD-4.0.0 | 2.06767E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.71186E-06 | 0 | 0 |
| K/Q | None | None | 0.998 | N | 0.655 | 0.291 | 0.322786055943 | gnomAD-4.0.0 | 1.61498E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.89548E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.2878 | likely_benign | 0.3264 | benign | 0.011 | Stabilizing | 0.994 | D | 0.577 | neutral | None | None | None | None | N |
| K/C | 0.8477 | likely_pathogenic | 0.8772 | pathogenic | -0.457 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| K/D | 0.4849 | ambiguous | 0.5281 | ambiguous | -0.352 | Destabilizing | 0.988 | D | 0.612 | neutral | None | None | None | None | N |
| K/E | 0.189 | likely_benign | 0.2131 | benign | -0.362 | Destabilizing | 0.619 | D | 0.315 | neutral | N | 0.496734259 | None | None | N |
| K/F | 0.8196 | likely_pathogenic | 0.8496 | pathogenic | -0.321 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| K/G | 0.4737 | ambiguous | 0.5032 | ambiguous | -0.12 | Destabilizing | 0.999 | D | 0.593 | neutral | None | None | None | None | N |
| K/H | 0.3882 | ambiguous | 0.4302 | ambiguous | -0.203 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| K/I | 0.3748 | ambiguous | 0.435 | ambiguous | 0.272 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| K/L | 0.4049 | ambiguous | 0.4565 | ambiguous | 0.272 | Stabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | N |
| K/M | 0.3056 | likely_benign | 0.3494 | ambiguous | -0.126 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | D | 0.61154186 | None | None | N |
| K/N | 0.3955 | ambiguous | 0.4372 | ambiguous | -0.024 | Destabilizing | 0.999 | D | 0.679 | prob.neutral | N | 0.512988263 | None | None | N |
| K/P | 0.4582 | ambiguous | 0.4861 | ambiguous | 0.208 | Stabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| K/Q | 0.1847 | likely_benign | 0.2082 | benign | -0.159 | Destabilizing | 0.998 | D | 0.655 | neutral | N | 0.494806517 | None | None | N |
| K/R | 0.1023 | likely_benign | 0.1067 | benign | -0.113 | Destabilizing | 0.992 | D | 0.536 | neutral | N | 0.502648973 | None | None | N |
| K/S | 0.3755 | ambiguous | 0.4177 | ambiguous | -0.365 | Destabilizing | 0.994 | D | 0.573 | neutral | None | None | None | None | N |
| K/T | 0.1558 | likely_benign | 0.1798 | benign | -0.259 | Destabilizing | 0.999 | D | 0.673 | neutral | N | 0.507482686 | None | None | N |
| K/V | 0.3111 | likely_benign | 0.3663 | ambiguous | 0.208 | Stabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| K/W | 0.8429 | likely_pathogenic | 0.8673 | pathogenic | -0.434 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| K/Y | 0.7394 | likely_pathogenic | 0.7819 | pathogenic | -0.083 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | 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.