Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25461 | 76606;76607;76608 | chr2:178569751;178569750;178569749 | chr2:179434478;179434477;179434476 |
| N2AB | 23820 | 71683;71684;71685 | chr2:178569751;178569750;178569749 | chr2:179434478;179434477;179434476 |
| N2A | 22893 | 68902;68903;68904 | chr2:178569751;178569750;178569749 | chr2:179434478;179434477;179434476 |
| N2B | 16396 | 49411;49412;49413 | chr2:178569751;178569750;178569749 | chr2:179434478;179434477;179434476 |
| Novex-1 | 16521 | 49786;49787;49788 | chr2:178569751;178569750;178569749 | chr2:179434478;179434477;179434476 |
| Novex-2 | 16588 | 49987;49988;49989 | chr2:178569751;178569750;178569749 | chr2:179434478;179434477;179434476 |
| 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/S | None | None | 0.998 | N | 0.671 | 0.46 | 0.799507715711 | gnomAD-4.0.0 | 6.84428E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99567E-07 | 0 | 0 |
| I/T | rs781399131  |
-2.262 | 0.989 | N | 0.613 | 0.374 | 0.637462270759 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.13E-05 | 0 |
| I/T | rs781399131 |
-2.262 | 0.989 | N | 0.613 | 0.374 | 0.637462270759 | gnomAD-4.0.0 | 4.791E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29697E-06 | 0 | 0 |
| I/V | rs1707455514 |
None | 0.333 | N | 0.268 | 0.085 | None | gnomAD-4.0.0 | 1.59248E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8593E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.364 | ambiguous | 0.3907 | ambiguous | -2.102 | Highly Destabilizing | 0.992 | D | 0.505 | neutral | None | None | None | None | N |
| I/C | 0.5259 | ambiguous | 0.5384 | ambiguous | -1.49 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | N |
| I/D | 0.6401 | likely_pathogenic | 0.6622 | pathogenic | -1.635 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| I/E | 0.4994 | ambiguous | 0.4987 | ambiguous | -1.519 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/F | 0.1366 | likely_benign | 0.1372 | benign | -1.278 | Destabilizing | 0.998 | D | 0.67 | neutral | N | 0.520596387 | None | None | N |
| I/G | 0.5948 | likely_pathogenic | 0.632 | pathogenic | -2.551 | Highly Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/H | 0.4862 | ambiguous | 0.4924 | ambiguous | -1.802 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| I/K | 0.3183 | likely_benign | 0.3193 | benign | -1.429 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| I/L | 0.088 | likely_benign | 0.0917 | benign | -0.874 | Destabilizing | 0.889 | D | 0.375 | neutral | N | 0.438575223 | None | None | N |
| I/M | 0.0861 | likely_benign | 0.0868 | benign | -0.839 | Destabilizing | 0.998 | D | 0.671 | neutral | N | 0.493485511 | None | None | N |
| I/N | 0.2542 | likely_benign | 0.268 | benign | -1.439 | Destabilizing | 0.999 | D | 0.757 | deleterious | N | 0.520844316 | None | None | N |
| I/P | 0.8695 | likely_pathogenic | 0.8708 | pathogenic | -1.256 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| I/Q | 0.3671 | ambiguous | 0.377 | ambiguous | -1.473 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| I/R | 0.2713 | likely_benign | 0.2713 | benign | -1.004 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| I/S | 0.3027 | likely_benign | 0.3276 | benign | -2.195 | Highly Destabilizing | 0.998 | D | 0.671 | neutral | N | 0.500738403 | None | None | N |
| I/T | 0.2428 | likely_benign | 0.2659 | benign | -1.944 | Destabilizing | 0.989 | D | 0.613 | neutral | N | 0.499335681 | None | None | N |
| I/V | 0.0753 | likely_benign | 0.0782 | benign | -1.256 | Destabilizing | 0.333 | N | 0.268 | neutral | N | 0.422472407 | None | None | N |
| I/W | 0.6537 | likely_pathogenic | 0.6506 | pathogenic | -1.453 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| I/Y | 0.4349 | ambiguous | 0.4365 | ambiguous | -1.199 | Destabilizing | 1.0 | D | 0.718 | 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.