Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24159 | 72700;72701;72702 | chr2:178573657;178573656;178573655 | chr2:179438384;179438383;179438382 |
| N2AB | 22518 | 67777;67778;67779 | chr2:178573657;178573656;178573655 | chr2:179438384;179438383;179438382 |
| N2A | 21591 | 64996;64997;64998 | chr2:178573657;178573656;178573655 | chr2:179438384;179438383;179438382 |
| N2B | 15094 | 45505;45506;45507 | chr2:178573657;178573656;178573655 | chr2:179438384;179438383;179438382 |
| Novex-1 | 15219 | 45880;45881;45882 | chr2:178573657;178573656;178573655 | chr2:179438384;179438383;179438382 |
| Novex-2 | 15286 | 46081;46082;46083 | chr2:178573657;178573656;178573655 | chr2:179438384;179438383;179438382 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs371764714  |
-1.827 | None | N | 0.246 | 0.057 | None | gnomAD-2.1.1 | 3.86E-05 | None | None | None | None | N | None | 2.56981E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.97E-05 | 0 |
| I/V | rs371764714 |
-1.827 | None | N | 0.246 | 0.057 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 1.68829E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/V | rs371764714 |
-1.827 | None | N | 0.246 | 0.057 | None | gnomAD-4.0.0 | 2.11103E-05 | None | None | None | None | N | None | 1.67103E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 1.58717E-05 | 0 | 3.43513E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2752 | likely_benign | 0.3616 | ambiguous | -2.656 | Highly Destabilizing | 0.035 | N | 0.583 | neutral | None | None | None | None | N |
| I/C | 0.644 | likely_pathogenic | 0.7039 | pathogenic | -1.736 | Destabilizing | 0.824 | D | 0.651 | neutral | None | None | None | None | N |
| I/D | 0.7476 | likely_pathogenic | 0.8034 | pathogenic | -3.081 | Highly Destabilizing | 0.555 | D | 0.682 | prob.neutral | None | None | None | None | N |
| I/E | 0.567 | likely_pathogenic | 0.6462 | pathogenic | -2.948 | Highly Destabilizing | 0.555 | D | 0.684 | prob.neutral | None | None | None | None | N |
| I/F | 0.2213 | likely_benign | 0.2746 | benign | -1.656 | Destabilizing | 0.38 | N | 0.647 | neutral | None | None | None | None | N |
| I/G | 0.7033 | likely_pathogenic | 0.797 | pathogenic | -3.099 | Highly Destabilizing | 0.555 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/H | 0.5648 | likely_pathogenic | 0.6321 | pathogenic | -2.476 | Highly Destabilizing | 0.935 | D | 0.691 | prob.neutral | None | None | None | None | N |
| I/K | 0.5102 | ambiguous | 0.5637 | ambiguous | -2.135 | Highly Destabilizing | 0.484 | N | 0.677 | prob.neutral | N | 0.4705422 | None | None | N |
| I/L | 0.1253 | likely_benign | 0.1436 | benign | -1.395 | Destabilizing | None | N | 0.281 | neutral | N | 0.46753043 | None | None | N |
| I/M | 0.1118 | likely_benign | 0.1293 | benign | -1.115 | Destabilizing | 0.317 | N | 0.637 | neutral | N | 0.49029595 | None | None | N |
| I/N | 0.3739 | ambiguous | 0.4405 | ambiguous | -2.233 | Highly Destabilizing | 0.791 | D | 0.694 | prob.neutral | None | None | None | None | N |
| I/P | 0.9692 | likely_pathogenic | 0.9767 | pathogenic | -1.797 | Destabilizing | 0.791 | D | 0.682 | prob.neutral | None | None | None | None | N |
| I/Q | 0.5022 | ambiguous | 0.5713 | pathogenic | -2.252 | Highly Destabilizing | 0.791 | D | 0.69 | prob.neutral | None | None | None | None | N |
| I/R | 0.3956 | ambiguous | 0.456 | ambiguous | -1.574 | Destabilizing | 0.484 | N | 0.696 | prob.neutral | N | 0.46705946 | None | None | N |
| I/S | 0.2699 | likely_benign | 0.355 | ambiguous | -2.814 | Highly Destabilizing | 0.38 | N | 0.643 | neutral | None | None | None | None | N |
| I/T | 0.112 | likely_benign | 0.1388 | benign | -2.574 | Highly Destabilizing | 0.062 | N | 0.603 | neutral | N | 0.46766597 | None | None | N |
| I/V | 0.0574 | likely_benign | 0.0668 | benign | -1.797 | Destabilizing | None | N | 0.246 | neutral | N | 0.4398074 | None | None | N |
| I/W | 0.8232 | likely_pathogenic | 0.8521 | pathogenic | -2.04 | Highly Destabilizing | 0.935 | D | 0.701 | prob.neutral | None | None | None | None | N |
| I/Y | 0.5836 | likely_pathogenic | 0.6498 | pathogenic | -1.848 | Destabilizing | 0.555 | D | 0.667 | 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.