Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23617 | 71074;71075;71076 | chr2:178575283;178575282;178575281 | chr2:179440010;179440009;179440008 |
| N2AB | 21976 | 66151;66152;66153 | chr2:178575283;178575282;178575281 | chr2:179440010;179440009;179440008 |
| N2A | 21049 | 63370;63371;63372 | chr2:178575283;178575282;178575281 | chr2:179440010;179440009;179440008 |
| N2B | 14552 | 43879;43880;43881 | chr2:178575283;178575282;178575281 | chr2:179440010;179440009;179440008 |
| Novex-1 | 14677 | 44254;44255;44256 | chr2:178575283;178575282;178575281 | chr2:179440010;179440009;179440008 |
| Novex-2 | 14744 | 44455;44456;44457 | chr2:178575283;178575282;178575281 | chr2:179440010;179440009;179440008 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | None | None | 0.639 | N | 0.554 | 0.149 | 0.207176502487 | gnomAD-4.0.0 | 1.59219E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85933E-06 | 0 | 0 |
| R/T | None | None | 0.973 | N | 0.653 | 0.331 | 0.459995458672 | gnomAD-4.0.0 | 1.59219E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85933E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6585 | likely_pathogenic | 0.6633 | pathogenic | -1.001 | Destabilizing | 0.979 | D | 0.573 | neutral | None | None | None | None | I |
| R/C | 0.3023 | likely_benign | 0.3038 | benign | -0.95 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | I |
| R/D | 0.9575 | likely_pathogenic | 0.9582 | pathogenic | -0.181 | Destabilizing | 0.129 | N | 0.47 | neutral | None | None | None | None | I |
| R/E | 0.7175 | likely_pathogenic | 0.7179 | pathogenic | -0.011 | Destabilizing | 0.877 | D | 0.545 | neutral | None | None | None | None | I |
| R/F | 0.8643 | likely_pathogenic | 0.8647 | pathogenic | -0.502 | Destabilizing | 0.998 | D | 0.674 | neutral | None | None | None | None | I |
| R/G | 0.6286 | likely_pathogenic | 0.6382 | pathogenic | -1.369 | Destabilizing | 0.973 | D | 0.588 | neutral | N | 0.47022256 | None | None | I |
| R/H | 0.3207 | likely_benign | 0.3198 | benign | -1.559 | Destabilizing | 0.998 | D | 0.658 | neutral | None | None | None | None | I |
| R/I | 0.5494 | ambiguous | 0.5531 | ambiguous | 0.015 | Stabilizing | 0.991 | D | 0.689 | prob.neutral | N | 0.482085845 | None | None | I |
| R/K | 0.1791 | likely_benign | 0.187 | benign | -1.029 | Destabilizing | 0.639 | D | 0.554 | neutral | N | 0.474839881 | None | None | I |
| R/L | 0.568 | likely_pathogenic | 0.581 | pathogenic | 0.015 | Stabilizing | 0.993 | D | 0.613 | neutral | None | None | None | None | I |
| R/M | 0.5429 | ambiguous | 0.54 | ambiguous | -0.414 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | I |
| R/N | 0.9159 | likely_pathogenic | 0.9167 | pathogenic | -0.599 | Destabilizing | 0.96 | D | 0.607 | neutral | None | None | None | None | I |
| R/P | 0.974 | likely_pathogenic | 0.9744 | pathogenic | -0.304 | Destabilizing | 0.997 | D | 0.696 | prob.neutral | None | None | None | None | I |
| R/Q | 0.182 | likely_benign | 0.1843 | benign | -0.62 | Destabilizing | 0.996 | D | 0.647 | neutral | None | None | None | None | I |
| R/S | 0.8076 | likely_pathogenic | 0.8077 | pathogenic | -1.39 | Destabilizing | 0.973 | D | 0.635 | neutral | N | 0.404157927 | None | None | I |
| R/T | 0.4927 | ambiguous | 0.5158 | ambiguous | -1.015 | Destabilizing | 0.973 | D | 0.653 | neutral | N | 0.493038853 | None | None | I |
| R/V | 0.5109 | ambiguous | 0.514 | ambiguous | -0.304 | Destabilizing | 0.99 | D | 0.693 | prob.neutral | None | None | None | None | I |
| R/W | 0.5063 | ambiguous | 0.4941 | ambiguous | -0.08 | Destabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | I |
| R/Y | 0.7832 | likely_pathogenic | 0.7779 | pathogenic | 0.153 | Stabilizing | 0.998 | D | 0.687 | prob.neutral | None | None | None | None | I |
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.