Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30888 | 92887;92888;92889 | chr2:178548964;178548963;178548962 | chr2:179413691;179413690;179413689 |
| N2AB | 29247 | 87964;87965;87966 | chr2:178548964;178548963;178548962 | chr2:179413691;179413690;179413689 |
| N2A | 28320 | 85183;85184;85185 | chr2:178548964;178548963;178548962 | chr2:179413691;179413690;179413689 |
| N2B | 21823 | 65692;65693;65694 | chr2:178548964;178548963;178548962 | chr2:179413691;179413690;179413689 |
| Novex-1 | 21948 | 66067;66068;66069 | chr2:178548964;178548963;178548962 | chr2:179413691;179413690;179413689 |
| Novex-2 | 22015 | 66268;66269;66270 | chr2:178548964;178548963;178548962 | chr2:179413691;179413690;179413689 |
| 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/E | None | None | 0.004 | N | 0.239 | 0.301 | 0.184867976434 | gnomAD-4.0.0 | 6.8418E-07 | None | None | None | None | N | None | 2.98793E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs1393497190  |
-0.438 | 0.549 | N | 0.401 | 0.272 | 0.258779203287 | 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 |
| A/V | rs1393497190 |
-0.438 | 0.549 | N | 0.401 | 0.272 | 0.258779203287 | gnomAD-4.0.0 | 2.05254E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99441E-07 | 0 | 3.31301E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4342 | ambiguous | 0.4197 | ambiguous | -0.727 | Destabilizing | 0.992 | D | 0.418 | neutral | None | None | None | None | N |
| A/D | 0.228 | likely_benign | 0.1992 | benign | -0.822 | Destabilizing | 0.447 | N | 0.429 | neutral | None | None | None | None | N |
| A/E | 0.1893 | likely_benign | 0.167 | benign | -0.986 | Destabilizing | 0.004 | N | 0.239 | neutral | N | 0.339664597 | None | None | N |
| A/F | 0.3304 | likely_benign | 0.3172 | benign | -1.089 | Destabilizing | 0.972 | D | 0.488 | neutral | None | None | None | None | N |
| A/G | 0.1397 | likely_benign | 0.1353 | benign | -0.496 | Destabilizing | 0.334 | N | 0.369 | neutral | N | 0.485851882 | None | None | N |
| A/H | 0.3985 | ambiguous | 0.3855 | ambiguous | -0.552 | Destabilizing | 0.977 | D | 0.473 | neutral | None | None | None | None | N |
| A/I | 0.1873 | likely_benign | 0.1728 | benign | -0.482 | Destabilizing | 0.92 | D | 0.441 | neutral | None | None | None | None | N |
| A/K | 0.4328 | ambiguous | 0.4097 | ambiguous | -0.784 | Destabilizing | 0.447 | N | 0.377 | neutral | None | None | None | None | N |
| A/L | 0.1574 | likely_benign | 0.1473 | benign | -0.482 | Destabilizing | 0.617 | D | 0.405 | neutral | None | None | None | None | N |
| A/M | 0.1781 | likely_benign | 0.1683 | benign | -0.371 | Destabilizing | 0.992 | D | 0.413 | neutral | None | None | None | None | N |
| A/N | 0.1981 | likely_benign | 0.1804 | benign | -0.399 | Destabilizing | 0.85 | D | 0.5 | neutral | None | None | None | None | N |
| A/P | 0.0881 | likely_benign | 0.0808 | benign | -0.434 | Destabilizing | 0.002 | N | 0.207 | neutral | N | 0.348443504 | None | None | N |
| A/Q | 0.2797 | likely_benign | 0.2604 | benign | -0.742 | Destabilizing | 0.739 | D | 0.429 | neutral | None | None | None | None | N |
| A/R | 0.4346 | ambiguous | 0.414 | ambiguous | -0.239 | Destabilizing | 0.85 | D | 0.435 | neutral | None | None | None | None | N |
| A/S | 0.0921 | likely_benign | 0.0883 | benign | -0.562 | Destabilizing | 0.045 | N | 0.279 | neutral | N | 0.43802065 | None | None | N |
| A/T | 0.0828 | likely_benign | 0.079 | benign | -0.657 | Destabilizing | 0.379 | N | 0.395 | neutral | N | 0.415663865 | None | None | N |
| A/V | 0.107 | likely_benign | 0.102 | benign | -0.434 | Destabilizing | 0.549 | D | 0.401 | neutral | N | 0.478675194 | None | None | N |
| A/W | 0.6654 | likely_pathogenic | 0.6527 | pathogenic | -1.21 | Destabilizing | 0.992 | D | 0.583 | neutral | None | None | None | None | N |
| A/Y | 0.4056 | ambiguous | 0.3949 | ambiguous | -0.874 | Destabilizing | 0.972 | D | 0.489 | 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.