Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25742 | 77449;77450;77451 | chr2:178568908;178568907;178568906 | chr2:179433635;179433634;179433633 |
| N2AB | 24101 | 72526;72527;72528 | chr2:178568908;178568907;178568906 | chr2:179433635;179433634;179433633 |
| N2A | 23174 | 69745;69746;69747 | chr2:178568908;178568907;178568906 | chr2:179433635;179433634;179433633 |
| N2B | 16677 | 50254;50255;50256 | chr2:178568908;178568907;178568906 | chr2:179433635;179433634;179433633 |
| Novex-1 | 16802 | 50629;50630;50631 | chr2:178568908;178568907;178568906 | chr2:179433635;179433634;179433633 |
| Novex-2 | 16869 | 50830;50831;50832 | chr2:178568908;178568907;178568906 | chr2:179433635;179433634;179433633 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs1707054015  |
None | 0.028 | N | 0.359 | 0.07 | 0.15556083564 | 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 |
| S/N | rs1707054015 |
None | 0.028 | N | 0.359 | 0.07 | 0.15556083564 | gnomAD-4.0.0 | 6.57505E-06 | None | None | None | None | N | None | 2.41243E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/R | rs753101927 |
-0.316 | 0.865 | N | 0.322 | 0.216 | 0.262175524916 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| S/R | rs753101927 |
-0.316 | 0.865 | N | 0.322 | 0.216 | 0.262175524916 | gnomAD-4.0.0 | 1.36885E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79928E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0817 | likely_benign | 0.0792 | benign | -0.306 | Destabilizing | 0.01 | N | 0.407 | neutral | None | None | None | None | N |
| S/C | 0.1174 | likely_benign | 0.118 | benign | -0.27 | Destabilizing | 0.929 | D | 0.406 | neutral | N | 0.507844011 | None | None | N |
| S/D | 0.3713 | ambiguous | 0.3472 | ambiguous | 0.047 | Stabilizing | 0.392 | N | 0.323 | neutral | None | None | None | None | N |
| S/E | 0.4618 | ambiguous | 0.4456 | ambiguous | -0.057 | Destabilizing | 0.311 | N | 0.337 | neutral | None | None | None | None | N |
| S/F | 0.2724 | likely_benign | 0.245 | benign | -0.928 | Destabilizing | 0.894 | D | 0.44 | neutral | None | None | None | None | N |
| S/G | 0.0922 | likely_benign | 0.0897 | benign | -0.398 | Destabilizing | 0.475 | N | 0.337 | neutral | N | 0.502066555 | None | None | N |
| S/H | 0.357 | ambiguous | 0.3274 | benign | -0.9 | Destabilizing | 0.017 | N | 0.35 | neutral | None | None | None | None | N |
| S/I | 0.2027 | likely_benign | 0.1988 | benign | -0.193 | Destabilizing | 0.762 | D | 0.429 | neutral | N | 0.500842572 | None | None | N |
| S/K | 0.5923 | likely_pathogenic | 0.561 | ambiguous | -0.499 | Destabilizing | 0.547 | D | 0.299 | neutral | None | None | None | None | N |
| S/L | 0.1025 | likely_benign | 0.1007 | benign | -0.193 | Destabilizing | 0.547 | D | 0.371 | neutral | None | None | None | None | N |
| S/M | 0.2015 | likely_benign | 0.1867 | benign | 0.043 | Stabilizing | 0.985 | D | 0.363 | neutral | None | None | None | None | N |
| S/N | 0.1507 | likely_benign | 0.1387 | benign | -0.185 | Destabilizing | 0.028 | N | 0.359 | neutral | N | 0.492446994 | None | None | N |
| S/P | 0.59 | likely_pathogenic | 0.5921 | pathogenic | -0.203 | Destabilizing | 0.821 | D | 0.341 | neutral | None | None | None | None | N |
| S/Q | 0.4467 | ambiguous | 0.4129 | ambiguous | -0.459 | Destabilizing | 0.179 | N | 0.294 | neutral | None | None | None | None | N |
| S/R | 0.5505 | ambiguous | 0.5091 | ambiguous | -0.264 | Destabilizing | 0.865 | D | 0.322 | neutral | N | 0.520692388 | None | None | N |
| S/T | 0.0759 | likely_benign | 0.0738 | benign | -0.297 | Destabilizing | None | N | 0.291 | neutral | N | 0.467377978 | None | None | N |
| S/V | 0.1819 | likely_benign | 0.1756 | benign | -0.203 | Destabilizing | 0.311 | N | 0.377 | neutral | None | None | None | None | N |
| S/W | 0.4029 | ambiguous | 0.3837 | ambiguous | -0.948 | Destabilizing | 0.995 | D | 0.617 | neutral | None | None | None | None | N |
| S/Y | 0.2581 | likely_benign | 0.2407 | benign | -0.668 | Destabilizing | 0.809 | D | 0.439 | 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.