Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27328 | 82207;82208;82209 | chr2:178564150;178564149;178564148 | chr2:179428877;179428876;179428875 |
| N2AB | 25687 | 77284;77285;77286 | chr2:178564150;178564149;178564148 | chr2:179428877;179428876;179428875 |
| N2A | 24760 | 74503;74504;74505 | chr2:178564150;178564149;178564148 | chr2:179428877;179428876;179428875 |
| N2B | 18263 | 55012;55013;55014 | chr2:178564150;178564149;178564148 | chr2:179428877;179428876;179428875 |
| Novex-1 | 18388 | 55387;55388;55389 | chr2:178564150;178564149;178564148 | chr2:179428877;179428876;179428875 |
| Novex-2 | 18455 | 55588;55589;55590 | chr2:178564150;178564149;178564148 | chr2:179428877;179428876;179428875 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs376541881  |
-0.525 | 0.999 | D | 0.444 | 0.433 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 1.66003E-04 |
| T/A | rs376541881 |
-0.525 | 0.999 | D | 0.444 | 0.433 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| T/A | rs376541881 |
-0.525 | 0.999 | D | 0.444 | 0.433 | None | gnomAD-4.0.0 | 4.02802E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.8315E-05 | 0 | 1.28102E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1161 | likely_benign | 0.1119 | benign | -0.38 | Destabilizing | 0.999 | D | 0.444 | neutral | D | 0.532808828 | None | None | N |
| T/C | 0.5246 | ambiguous | 0.5486 | ambiguous | -0.273 | Destabilizing | 1.0 | D | 0.616 | neutral | None | None | None | None | N |
| T/D | 0.2956 | likely_benign | 0.2933 | benign | 0.438 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| T/E | 0.4287 | ambiguous | 0.41 | ambiguous | 0.374 | Stabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| T/F | 0.4222 | ambiguous | 0.419 | ambiguous | -0.855 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| T/G | 0.1923 | likely_benign | 0.2 | benign | -0.518 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | N |
| T/H | 0.3646 | ambiguous | 0.3631 | ambiguous | -0.775 | Destabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | N |
| T/I | 0.4369 | ambiguous | 0.4211 | ambiguous | -0.136 | Destabilizing | 1.0 | D | 0.667 | neutral | N | 0.486835327 | None | None | N |
| T/K | 0.3884 | ambiguous | 0.3666 | ambiguous | -0.258 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| T/L | 0.1941 | likely_benign | 0.1928 | benign | -0.136 | Destabilizing | 0.999 | D | 0.572 | neutral | None | None | None | None | N |
| T/M | 0.1579 | likely_benign | 0.156 | benign | -0.008 | Destabilizing | 1.0 | D | 0.63 | neutral | None | None | None | None | N |
| T/N | 0.1124 | likely_benign | 0.1152 | benign | -0.111 | Destabilizing | 1.0 | D | 0.672 | neutral | N | 0.483895584 | None | None | N |
| T/P | 0.5392 | ambiguous | 0.4385 | ambiguous | -0.188 | Destabilizing | 1.0 | D | 0.664 | neutral | N | 0.521068827 | None | None | N |
| T/Q | 0.3667 | ambiguous | 0.3684 | ambiguous | -0.294 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| T/R | 0.3349 | likely_benign | 0.3097 | benign | -0.032 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| T/S | 0.0847 | likely_benign | 0.0901 | benign | -0.367 | Destabilizing | 0.999 | D | 0.435 | neutral | D | 0.533558189 | None | None | N |
| T/V | 0.2811 | likely_benign | 0.2741 | benign | -0.188 | Destabilizing | 0.999 | D | 0.501 | neutral | None | None | None | None | N |
| T/W | 0.7546 | likely_pathogenic | 0.7388 | pathogenic | -0.858 | Destabilizing | 1.0 | D | 0.622 | neutral | None | None | None | None | N |
| T/Y | 0.4591 | ambiguous | 0.4591 | ambiguous | -0.565 | Destabilizing | 1.0 | D | 0.673 | 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.