Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25238 | 75937;75938;75939 | chr2:178570420;178570419;178570418 | chr2:179435147;179435146;179435145 |
| N2AB | 23597 | 71014;71015;71016 | chr2:178570420;178570419;178570418 | chr2:179435147;179435146;179435145 |
| N2A | 22670 | 68233;68234;68235 | chr2:178570420;178570419;178570418 | chr2:179435147;179435146;179435145 |
| N2B | 16173 | 48742;48743;48744 | chr2:178570420;178570419;178570418 | chr2:179435147;179435146;179435145 |
| Novex-1 | 16298 | 49117;49118;49119 | chr2:178570420;178570419;178570418 | chr2:179435147;179435146;179435145 |
| Novex-2 | 16365 | 49318;49319;49320 | chr2:178570420;178570419;178570418 | chr2:179435147;179435146;179435145 |
| 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/K | None | None | 0.007 | N | 0.29 | 0.187 | 0.438913950225 | gnomAD-4.0.0 | 2.73782E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59837E-06 | 0 | 0 |
| I/M | rs1473998672  |
-0.228 | None | N | 0.135 | 0.02 | 0.298403945805 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| I/M | rs1473998672 |
-0.228 | None | N | 0.135 | 0.02 | 0.298403945805 | gnomAD-4.0.0 | 9.55569E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41663E-04 | 2.85953E-06 | 0 | 1.21087E-04 |
| I/V | rs1265824976 |
None | 0.003 | N | 0.142 | 0.155 | 0.354183961838 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1265824976 |
None | 0.003 | N | 0.142 | 0.155 | 0.354183961838 | gnomAD-4.0.0 | 6.57471E-06 | None | None | None | None | I | None | 2.41196E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.147 | likely_benign | 0.141 | benign | -0.93 | Destabilizing | 0.002 | N | 0.151 | neutral | None | None | None | None | I |
| I/C | 0.3858 | ambiguous | 0.4035 | ambiguous | -0.555 | Destabilizing | 0.245 | N | 0.255 | neutral | None | None | None | None | I |
| I/D | 0.3525 | ambiguous | 0.3528 | ambiguous | -0.672 | Destabilizing | 0.018 | N | 0.331 | neutral | None | None | None | None | I |
| I/E | 0.2732 | likely_benign | 0.2804 | benign | -0.767 | Destabilizing | 0.009 | N | 0.291 | neutral | None | None | None | None | I |
| I/F | 0.1401 | likely_benign | 0.1384 | benign | -0.891 | Destabilizing | 0.022 | N | 0.195 | neutral | None | None | None | None | I |
| I/G | 0.3084 | likely_benign | 0.3078 | benign | -1.12 | Destabilizing | 0.009 | N | 0.296 | neutral | None | None | None | None | I |
| I/H | 0.2656 | likely_benign | 0.2641 | benign | -0.388 | Destabilizing | 0.245 | N | 0.302 | neutral | None | None | None | None | I |
| I/K | 0.1841 | likely_benign | 0.1992 | benign | -0.62 | Destabilizing | 0.007 | N | 0.29 | neutral | N | 0.442154246 | None | None | I |
| I/L | 0.0772 | likely_benign | 0.0779 | benign | -0.54 | Destabilizing | None | N | 0.035 | neutral | N | 0.378430842 | None | None | I |
| I/M | 0.0747 | likely_benign | 0.0765 | benign | -0.391 | Destabilizing | None | N | 0.135 | neutral | N | 0.450544443 | None | None | I |
| I/N | 0.1091 | likely_benign | 0.1083 | benign | -0.333 | Destabilizing | 0.018 | N | 0.378 | neutral | None | None | None | None | I |
| I/P | 0.7752 | likely_pathogenic | 0.7591 | pathogenic | -0.637 | Destabilizing | 0.085 | N | 0.419 | neutral | None | None | None | None | I |
| I/Q | 0.1936 | likely_benign | 0.1965 | benign | -0.615 | Destabilizing | 0.001 | N | 0.18 | neutral | None | None | None | None | I |
| I/R | 0.1667 | likely_benign | 0.1713 | benign | 0.049 | Stabilizing | 0.017 | N | 0.422 | neutral | N | 0.43603635 | None | None | I |
| I/S | 0.0931 | likely_benign | 0.0889 | benign | -0.755 | Destabilizing | None | N | 0.075 | neutral | None | None | None | None | I |
| I/T | 0.0724 | likely_benign | 0.0656 | benign | -0.748 | Destabilizing | None | N | 0.1 | neutral | N | 0.329924819 | None | None | I |
| I/V | 0.0674 | likely_benign | 0.0685 | benign | -0.637 | Destabilizing | 0.003 | N | 0.142 | neutral | N | 0.440730094 | None | None | I |
| I/W | 0.6382 | likely_pathogenic | 0.618 | pathogenic | -0.9 | Destabilizing | 0.788 | D | 0.277 | neutral | None | None | None | None | I |
| I/Y | 0.3599 | ambiguous | 0.3538 | ambiguous | -0.675 | Destabilizing | 0.085 | N | 0.346 | 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.