Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2383 | 7372;7373;7374 | chr2:178774021;178774020;178774019 | chr2:179638748;179638747;179638746 |
| N2AB | 2383 | 7372;7373;7374 | chr2:178774021;178774020;178774019 | chr2:179638748;179638747;179638746 |
| N2A | 2383 | 7372;7373;7374 | chr2:178774021;178774020;178774019 | chr2:179638748;179638747;179638746 |
| N2B | 2337 | 7234;7235;7236 | chr2:178774021;178774020;178774019 | chr2:179638748;179638747;179638746 |
| Novex-1 | 2337 | 7234;7235;7236 | chr2:178774021;178774020;178774019 | chr2:179638748;179638747;179638746 |
| Novex-2 | 2337 | 7234;7235;7236 | chr2:178774021;178774020;178774019 | chr2:179638748;179638747;179638746 |
| Novex-3 | 2383 | 7372;7373;7374 | chr2:178774021;178774020;178774019 | chr2:179638748;179638747;179638746 |
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/I | None | None | 0.013 | N | 0.288 | 0.15 | 0.425970041486 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| S/N | rs2091903578  |
None | None | N | 0.07 | 0.151 | 0.0716867268079 | 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 |
| S/N | rs2091903578 |
None | None | N | 0.07 | 0.151 | 0.0716867268079 | gnomAD-4.0.0 | 2.02979E-06 | None | None | None | None | I | None | 1.74685E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.2049E-06 | 0 | 0 |
| S/R | rs770123979 |
0.132 | 0.001 | N | 0.253 | 0.17 | 0.0716867268079 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.82E-06 | 0 |
| S/R | rs770123979 |
0.132 | 0.001 | N | 0.253 | 0.17 | 0.0716867268079 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92604E-04 | None | 0 | 0 | 0 | 2.07125E-04 | 4.78011E-04 |
| S/R | rs770123979 |
0.132 | 0.001 | N | 0.253 | 0.17 | 0.0716867268079 | gnomAD-4.0.0 | 6.81487E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.22886E-05 | None | 0 | 0 | 5.0848E-06 | 2.19587E-05 | 3.1998E-05 |
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 | 0.0982 | likely_benign | 0.1003 | benign | -0.085 | Destabilizing | None | N | 0.143 | neutral | None | None | None | None | I |
| S/C | 0.1527 | likely_benign | 0.1543 | benign | -0.31 | Destabilizing | 0.258 | N | 0.417 | neutral | N | 0.484890757 | None | None | I |
| S/D | 0.1244 | likely_benign | 0.1263 | benign | 0.033 | Stabilizing | None | N | 0.166 | neutral | None | None | None | None | I |
| S/E | 0.2711 | likely_benign | 0.2879 | benign | -0.059 | Destabilizing | None | N | 0.181 | neutral | None | None | None | None | I |
| S/F | 0.3385 | likely_benign | 0.3547 | ambiguous | -0.764 | Destabilizing | 0.051 | N | 0.341 | neutral | None | None | None | None | I |
| S/G | 0.0744 | likely_benign | 0.0758 | benign | -0.163 | Destabilizing | None | N | 0.071 | neutral | N | 0.397166012 | None | None | I |
| S/H | 0.161 | likely_benign | 0.1559 | benign | -0.485 | Destabilizing | 0.009 | N | 0.35 | neutral | None | None | None | None | I |
| S/I | 0.209 | likely_benign | 0.2157 | benign | -0.012 | Destabilizing | 0.013 | N | 0.288 | neutral | N | 0.499667311 | None | None | I |
| S/K | 0.305 | likely_benign | 0.3078 | benign | -0.367 | Destabilizing | None | N | 0.075 | neutral | None | None | None | None | I |
| S/L | 0.1755 | likely_benign | 0.1834 | benign | -0.012 | Destabilizing | 0.002 | N | 0.242 | neutral | None | None | None | None | I |
| S/M | 0.1917 | likely_benign | 0.1922 | benign | -0.132 | Destabilizing | 0.116 | N | 0.468 | neutral | None | None | None | None | I |
| S/N | 0.0463 | likely_benign | 0.045 | benign | -0.082 | Destabilizing | None | N | 0.07 | neutral | N | 0.327413837 | None | None | I |
| S/P | 0.3766 | ambiguous | 0.4487 | ambiguous | -0.009 | Destabilizing | 0.008 | N | 0.241 | neutral | None | None | None | None | I |
| S/Q | 0.2872 | likely_benign | 0.2885 | benign | -0.283 | Destabilizing | 0.001 | N | 0.21 | neutral | None | None | None | None | I |
| S/R | 0.3368 | likely_benign | 0.4133 | ambiguous | -0.116 | Destabilizing | 0.001 | N | 0.253 | neutral | N | 0.462599018 | None | None | I |
| S/T | 0.0833 | likely_benign | 0.0818 | benign | -0.151 | Destabilizing | None | N | 0.189 | neutral | N | 0.455171793 | None | None | I |
| S/V | 0.2177 | likely_benign | 0.225 | benign | -0.009 | Destabilizing | 0.002 | N | 0.234 | neutral | None | None | None | None | I |
| S/W | 0.4509 | ambiguous | 0.4757 | ambiguous | -0.875 | Destabilizing | 0.316 | N | 0.401 | neutral | None | None | None | None | I |
| S/Y | 0.169 | likely_benign | 0.1704 | benign | -0.542 | Destabilizing | 0.051 | N | 0.305 | 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.