Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21651 | 65176;65177;65178 | chr2:178584690;178584689;178584688 | chr2:179449417;179449416;179449415 |
| N2AB | 20010 | 60253;60254;60255 | chr2:178584690;178584689;178584688 | chr2:179449417;179449416;179449415 |
| N2A | 19083 | 57472;57473;57474 | chr2:178584690;178584689;178584688 | chr2:179449417;179449416;179449415 |
| N2B | 12586 | 37981;37982;37983 | chr2:178584690;178584689;178584688 | chr2:179449417;179449416;179449415 |
| Novex-1 | 12711 | 38356;38357;38358 | chr2:178584690;178584689;178584688 | chr2:179449417;179449416;179449415 |
| Novex-2 | 12778 | 38557;38558;38559 | chr2:178584690;178584689;178584688 | chr2:179449417;179449416;179449415 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/R | rs2048549278  |
None | 0.976 | N | 0.57 | 0.275 | 0.604527667468 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/R | rs2048549278 |
None | 0.976 | N | 0.57 | 0.275 | 0.604527667468 | gnomAD-4.0.0 | 6.57635E-06 | None | None | None | None | N | None | 2.41289E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs2048549278 |
None | 0.651 | N | 0.513 | 0.251 | 0.692295424123 | gnomAD-4.0.0 | 1.36869E-06 | None | None | None | None | N | None | 5.9805E-05 | 0 | None | 0 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5862 | likely_pathogenic | 0.5916 | pathogenic | -2.442 | Highly Destabilizing | 0.505 | D | 0.469 | neutral | None | None | None | None | N |
| M/C | 0.7559 | likely_pathogenic | 0.7477 | pathogenic | -2.176 | Highly Destabilizing | 0.995 | D | 0.521 | neutral | None | None | None | None | N |
| M/D | 0.9792 | likely_pathogenic | 0.9809 | pathogenic | -1.557 | Destabilizing | 0.982 | D | 0.626 | neutral | None | None | None | None | N |
| M/E | 0.8613 | likely_pathogenic | 0.8693 | pathogenic | -1.364 | Destabilizing | 0.982 | D | 0.604 | neutral | None | None | None | None | N |
| M/F | 0.4657 | ambiguous | 0.4624 | ambiguous | -0.934 | Destabilizing | 0.712 | D | 0.505 | neutral | None | None | None | None | N |
| M/G | 0.8971 | likely_pathogenic | 0.9012 | pathogenic | -2.902 | Highly Destabilizing | 0.939 | D | 0.65 | prob.neutral | None | None | None | None | N |
| M/H | 0.82 | likely_pathogenic | 0.8444 | pathogenic | -2.017 | Highly Destabilizing | 0.995 | D | 0.566 | neutral | None | None | None | None | N |
| M/I | 0.3049 | likely_benign | 0.2703 | benign | -1.137 | Destabilizing | 0.002 | N | 0.116 | neutral | N | 0.434798626 | None | None | N |
| M/K | 0.546 | ambiguous | 0.5682 | pathogenic | -1.427 | Destabilizing | 0.791 | D | 0.608 | neutral | N | 0.506989585 | None | None | N |
| M/L | 0.1829 | likely_benign | 0.1702 | benign | -1.137 | Destabilizing | 0.068 | N | 0.271 | neutral | N | 0.469372559 | None | None | N |
| M/N | 0.8695 | likely_pathogenic | 0.874 | pathogenic | -1.694 | Destabilizing | 0.982 | D | 0.597 | neutral | None | None | None | None | N |
| M/P | 0.984 | likely_pathogenic | 0.9847 | pathogenic | -1.553 | Destabilizing | 0.982 | D | 0.597 | neutral | None | None | None | None | N |
| M/Q | 0.5885 | likely_pathogenic | 0.6164 | pathogenic | -1.491 | Destabilizing | 0.982 | D | 0.483 | neutral | None | None | None | None | N |
| M/R | 0.5602 | ambiguous | 0.5931 | pathogenic | -1.217 | Destabilizing | 0.976 | D | 0.57 | neutral | N | 0.517763939 | None | None | N |
| M/S | 0.786 | likely_pathogenic | 0.7874 | pathogenic | -2.363 | Highly Destabilizing | 0.834 | D | 0.537 | neutral | None | None | None | None | N |
| M/T | 0.3761 | ambiguous | 0.381 | ambiguous | -2.036 | Highly Destabilizing | 0.651 | D | 0.513 | neutral | N | 0.476146603 | None | None | N |
| M/V | 0.1007 | likely_benign | 0.0917 | benign | -1.553 | Destabilizing | 0.144 | N | 0.321 | neutral | N | 0.428389941 | None | None | N |
| M/W | 0.8597 | likely_pathogenic | 0.8796 | pathogenic | -1.048 | Destabilizing | 0.995 | D | 0.531 | neutral | None | None | None | None | N |
| M/Y | 0.7688 | likely_pathogenic | 0.7966 | pathogenic | -1.1 | Destabilizing | 0.982 | D | 0.569 | 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.