Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31973 | 96142;96143;96144 | chr2:178544312;178544311;178544310 | chr2:179409039;179409038;179409037 |
| N2AB | 30332 | 91219;91220;91221 | chr2:178544312;178544311;178544310 | chr2:179409039;179409038;179409037 |
| N2A | 29405 | 88438;88439;88440 | chr2:178544312;178544311;178544310 | chr2:179409039;179409038;179409037 |
| N2B | 22908 | 68947;68948;68949 | chr2:178544312;178544311;178544310 | chr2:179409039;179409038;179409037 |
| Novex-1 | 23033 | 69322;69323;69324 | chr2:178544312;178544311;178544310 | chr2:179409039;179409038;179409037 |
| Novex-2 | 23100 | 69523;69524;69525 | chr2:178544312;178544311;178544310 | chr2:179409039;179409038;179409037 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs377462274  |
-0.333 | 0.012 | N | 0.276 | 0.091 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| P/L | rs377462274 |
-0.333 | 0.012 | N | 0.276 | 0.091 | 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 |
| P/L | rs377462274 |
-0.333 | 0.012 | N | 0.276 | 0.091 | None | gnomAD-4.0.0 | 6.57402E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47003E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0681 | likely_benign | 0.069 | benign | -0.605 | Destabilizing | None | N | 0.177 | neutral | N | 0.434844272 | None | None | N |
| P/C | 0.2978 | likely_benign | 0.2888 | benign | -0.791 | Destabilizing | 0.356 | N | 0.471 | neutral | None | None | None | None | N |
| P/D | 0.3152 | likely_benign | 0.3106 | benign | -0.339 | Destabilizing | 0.072 | N | 0.404 | neutral | None | None | None | None | N |
| P/E | 0.2168 | likely_benign | 0.2178 | benign | -0.438 | Destabilizing | 0.072 | N | 0.405 | neutral | None | None | None | None | N |
| P/F | 0.3754 | ambiguous | 0.3557 | ambiguous | -0.724 | Destabilizing | 0.214 | N | 0.485 | neutral | None | None | None | None | N |
| P/G | 0.1691 | likely_benign | 0.1627 | benign | -0.753 | Destabilizing | 0.016 | N | 0.319 | neutral | None | None | None | None | N |
| P/H | 0.1485 | likely_benign | 0.1437 | benign | -0.242 | Destabilizing | 0.628 | D | 0.47 | neutral | None | None | None | None | N |
| P/I | 0.2251 | likely_benign | 0.2108 | benign | -0.357 | Destabilizing | 0.016 | N | 0.393 | neutral | None | None | None | None | N |
| P/K | 0.1563 | likely_benign | 0.1493 | benign | -0.582 | Destabilizing | 0.072 | N | 0.398 | neutral | None | None | None | None | N |
| P/L | 0.1038 | likely_benign | 0.0991 | benign | -0.357 | Destabilizing | 0.012 | N | 0.276 | neutral | N | 0.45089116 | None | None | N |
| P/M | 0.1922 | likely_benign | 0.1772 | benign | -0.462 | Destabilizing | 0.356 | N | 0.481 | neutral | None | None | None | None | N |
| P/N | 0.1835 | likely_benign | 0.1732 | benign | -0.386 | Destabilizing | 0.072 | N | 0.491 | neutral | None | None | None | None | N |
| P/Q | 0.13 | likely_benign | 0.1255 | benign | -0.608 | Destabilizing | 0.295 | N | 0.534 | neutral | N | 0.42445392 | None | None | N |
| P/R | 0.1346 | likely_benign | 0.1278 | benign | -0.047 | Destabilizing | 0.055 | N | 0.499 | neutral | N | 0.421221614 | None | None | N |
| P/S | 0.0938 | likely_benign | 0.0902 | benign | -0.771 | Destabilizing | 0.012 | N | 0.301 | neutral | N | 0.351860316 | None | None | N |
| P/T | 0.0677 | likely_benign | 0.0614 | benign | -0.765 | Destabilizing | None | N | 0.176 | neutral | N | 0.337082864 | None | None | N |
| P/V | 0.1565 | likely_benign | 0.1515 | benign | -0.405 | Destabilizing | None | N | 0.257 | neutral | None | None | None | None | N |
| P/W | 0.5155 | ambiguous | 0.49 | ambiguous | -0.794 | Destabilizing | 0.864 | D | 0.499 | neutral | None | None | None | None | N |
| P/Y | 0.3324 | likely_benign | 0.3128 | benign | -0.511 | Destabilizing | 0.356 | N | 0.483 | 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.