Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22935 | 69028;69029;69030 | chr2:178577623;178577622;178577621 | chr2:179442350;179442349;179442348 |
| N2AB | 21294 | 64105;64106;64107 | chr2:178577623;178577622;178577621 | chr2:179442350;179442349;179442348 |
| N2A | 20367 | 61324;61325;61326 | chr2:178577623;178577622;178577621 | chr2:179442350;179442349;179442348 |
| N2B | 13870 | 41833;41834;41835 | chr2:178577623;178577622;178577621 | chr2:179442350;179442349;179442348 |
| Novex-1 | 13995 | 42208;42209;42210 | chr2:178577623;178577622;178577621 | chr2:179442350;179442349;179442348 |
| Novex-2 | 14062 | 42409;42410;42411 | chr2:178577623;178577622;178577621 | chr2:179442350;179442349;179442348 |
| 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/N | rs971232021  |
-2.182 | 0.57 | N | 0.747 | 0.451 | 0.801932788065 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | N | None | 6.5E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/N | rs971232021 |
-2.182 | 0.57 | N | 0.747 | 0.451 | 0.801932788065 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/N | rs971232021 |
-2.182 | 0.57 | N | 0.747 | 0.451 | 0.801932788065 | gnomAD-4.0.0 | 3.87447E-06 | None | None | None | None | N | None | 3.39824E-05 | 0 | None | 0 | 2.43736E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5235 | ambiguous | 0.5393 | ambiguous | -2.079 | Highly Destabilizing | 0.016 | N | 0.556 | neutral | None | None | None | None | N |
| I/C | 0.7419 | likely_pathogenic | 0.764 | pathogenic | -1.401 | Destabilizing | 0.685 | D | 0.611 | neutral | None | None | None | None | N |
| I/D | 0.9388 | likely_pathogenic | 0.944 | pathogenic | -2.033 | Highly Destabilizing | 0.366 | N | 0.752 | deleterious | None | None | None | None | N |
| I/E | 0.8481 | likely_pathogenic | 0.8609 | pathogenic | -1.822 | Destabilizing | 0.366 | N | 0.74 | deleterious | None | None | None | None | N |
| I/F | 0.2832 | likely_benign | 0.2941 | benign | -1.193 | Destabilizing | 0.177 | N | 0.65 | prob.neutral | N | 0.47270823 | None | None | N |
| I/G | 0.8599 | likely_pathogenic | 0.8699 | pathogenic | -2.586 | Highly Destabilizing | 0.366 | N | 0.731 | deleterious | None | None | None | None | N |
| I/H | 0.7533 | likely_pathogenic | 0.7591 | pathogenic | -1.813 | Destabilizing | 0.869 | D | 0.722 | deleterious | None | None | None | None | N |
| I/K | 0.632 | likely_pathogenic | 0.6494 | pathogenic | -1.583 | Destabilizing | 0.366 | N | 0.74 | deleterious | None | None | None | None | N |
| I/L | 0.1242 | likely_benign | 0.1317 | benign | -0.64 | Destabilizing | None | N | 0.145 | neutral | N | 0.502583843 | None | None | N |
| I/M | 0.1368 | likely_benign | 0.1368 | benign | -0.602 | Destabilizing | 0.177 | N | 0.663 | prob.neutral | N | 0.491484048 | None | None | N |
| I/N | 0.5982 | likely_pathogenic | 0.5979 | pathogenic | -1.942 | Destabilizing | 0.57 | D | 0.747 | deleterious | N | 0.503093843 | None | None | N |
| I/P | 0.9562 | likely_pathogenic | 0.9614 | pathogenic | -1.098 | Destabilizing | 0.366 | N | 0.753 | deleterious | None | None | None | None | N |
| I/Q | 0.7016 | likely_pathogenic | 0.7154 | pathogenic | -1.803 | Destabilizing | 0.637 | D | 0.727 | deleterious | None | None | None | None | N |
| I/R | 0.5517 | ambiguous | 0.5703 | pathogenic | -1.323 | Destabilizing | 0.366 | N | 0.753 | deleterious | None | None | None | None | N |
| I/S | 0.6037 | likely_pathogenic | 0.6151 | pathogenic | -2.639 | Highly Destabilizing | 0.177 | N | 0.658 | prob.neutral | N | 0.500051969 | None | None | N |
| I/T | 0.4092 | ambiguous | 0.3994 | ambiguous | -2.271 | Highly Destabilizing | 0.03 | N | 0.621 | neutral | N | 0.482708182 | None | None | N |
| I/V | 0.0671 | likely_benign | 0.065 | benign | -1.098 | Destabilizing | None | N | 0.127 | neutral | N | 0.472644938 | None | None | N |
| I/W | 0.9137 | likely_pathogenic | 0.9167 | pathogenic | -1.468 | Destabilizing | 0.869 | D | 0.748 | deleterious | None | None | None | None | N |
| I/Y | 0.6816 | likely_pathogenic | 0.699 | pathogenic | -1.15 | Destabilizing | 0.366 | N | 0.7 | 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.