Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3864 | 11815;11816;11817 | chr2:178741643;178741642;178741641 | chr2:179606370;179606369;179606368 |
| N2AB | 3547 | 10864;10865;10866 | chr2:178741643;178741642;178741641 | chr2:179606370;179606369;179606368 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3501 | 10726;10727;10728 | chr2:178741643;178741642;178741641 | chr2:179606370;179606369;179606368 |
| Novex-1 | 3626 | 11101;11102;11103 | chr2:178741643;178741642;178741641 | chr2:179606370;179606369;179606368 |
| Novex-2 | 3693 | 11302;11303;11304 | chr2:178741643;178741642;178741641 | chr2:179606370;179606369;179606368 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs748910775  |
0.091 | 0.001 | N | 0.232 | 0.08 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/P | rs748910775 |
0.091 | 0.001 | N | 0.232 | 0.08 | None | gnomAD-4.0.0 | 6.84199E-07 | None | None | None | None | N | None | 0 | 2.23634E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs748910775 |
None | None | N | 0.145 | 0.024 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs748910775 |
None | None | N | 0.145 | 0.024 | None | gnomAD-4.0.0 | 4.33793E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93331E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5996 | likely_pathogenic | 0.5224 | ambiguous | -0.837 | Destabilizing | 0.667 | D | 0.257 | neutral | None | None | None | None | N |
| A/D | 0.3106 | likely_benign | 0.2226 | benign | -0.309 | Destabilizing | 0.175 | N | 0.302 | neutral | N | 0.400529011 | None | None | N |
| A/E | 0.2744 | likely_benign | 0.2052 | benign | -0.438 | Destabilizing | 0.22 | N | 0.287 | neutral | None | None | None | None | N |
| A/F | 0.4521 | ambiguous | 0.3091 | benign | -0.755 | Destabilizing | 0.497 | N | 0.328 | neutral | None | None | None | None | N |
| A/G | 0.1878 | likely_benign | 0.1518 | benign | -0.283 | Destabilizing | None | N | 0.151 | neutral | N | 0.40202218 | None | None | N |
| A/H | 0.5578 | ambiguous | 0.4407 | ambiguous | -0.179 | Destabilizing | 0.859 | D | 0.289 | neutral | None | None | None | None | N |
| A/I | 0.2666 | likely_benign | 0.1978 | benign | -0.277 | Destabilizing | 0.124 | N | 0.351 | neutral | None | None | None | None | N |
| A/K | 0.426 | ambiguous | 0.3046 | benign | -0.573 | Destabilizing | 0.22 | N | 0.289 | neutral | None | None | None | None | N |
| A/L | 0.2223 | likely_benign | 0.1667 | benign | -0.277 | Destabilizing | 0.02 | N | 0.341 | neutral | None | None | None | None | N |
| A/M | 0.2429 | likely_benign | 0.1905 | benign | -0.534 | Destabilizing | 0.025 | N | 0.261 | neutral | None | None | None | None | N |
| A/N | 0.2925 | likely_benign | 0.2142 | benign | -0.309 | Destabilizing | 0.22 | N | 0.295 | neutral | None | None | None | None | N |
| A/P | 0.1828 | likely_benign | 0.157 | benign | -0.231 | Destabilizing | 0.001 | N | 0.232 | neutral | N | 0.403900692 | None | None | N |
| A/Q | 0.3745 | ambiguous | 0.3033 | benign | -0.522 | Destabilizing | 0.667 | D | 0.352 | neutral | None | None | None | None | N |
| A/R | 0.3474 | ambiguous | 0.262 | benign | -0.156 | Destabilizing | 0.22 | N | 0.341 | neutral | None | None | None | None | N |
| A/S | 0.1061 | likely_benign | 0.0939 | benign | -0.548 | Destabilizing | 0.001 | N | 0.128 | neutral | N | 0.3467986 | None | None | N |
| A/T | 0.0946 | likely_benign | 0.0765 | benign | -0.588 | Destabilizing | None | N | 0.145 | neutral | N | 0.43298416 | None | None | N |
| A/V | 0.1324 | likely_benign | 0.1067 | benign | -0.231 | Destabilizing | 0.042 | N | 0.233 | neutral | N | 0.442207274 | None | None | N |
| A/W | 0.7991 | likely_pathogenic | 0.6954 | pathogenic | -0.891 | Destabilizing | 0.958 | D | 0.326 | neutral | None | None | None | None | N |
| A/Y | 0.5902 | likely_pathogenic | 0.4462 | ambiguous | -0.555 | Destabilizing | 0.667 | D | 0.309 | 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.