Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19694 | 59305;59306;59307 | chr2:178593039;178593038;178593037 | chr2:179457766;179457765;179457764 |
| N2AB | 18053 | 54382;54383;54384 | chr2:178593039;178593038;178593037 | chr2:179457766;179457765;179457764 |
| N2A | 17126 | 51601;51602;51603 | chr2:178593039;178593038;178593037 | chr2:179457766;179457765;179457764 |
| N2B | 10629 | 32110;32111;32112 | chr2:178593039;178593038;178593037 | chr2:179457766;179457765;179457764 |
| Novex-1 | 10754 | 32485;32486;32487 | chr2:178593039;178593038;178593037 | chr2:179457766;179457765;179457764 |
| Novex-2 | 10821 | 32686;32687;32688 | chr2:178593039;178593038;178593037 | chr2:179457766;179457765;179457764 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/Y | rs727505276  |
-0.724 | 0.096 | N | 0.551 | 0.186 | None | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | N | None | 2.47954E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| C/Y | rs727505276 |
-0.724 | 0.096 | N | 0.551 | 0.186 | None | gnomAD-3.1.2 | 1.05238E-04 | None | None | None | None | N | None | 3.86324E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/Y | rs727505276 |
-0.724 | 0.096 | N | 0.551 | 0.186 | None | gnomAD-4.0.0 | 1.92156E-05 | None | None | None | None | N | None | 4.14073E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.1689 | likely_benign | 0.1249 | benign | -0.523 | Destabilizing | 0.025 | N | 0.195 | neutral | None | None | None | None | N |
| C/D | 0.4866 | ambiguous | 0.3663 | ambiguous | -0.301 | Destabilizing | 0.104 | N | 0.479 | neutral | None | None | None | None | N |
| C/E | 0.3997 | ambiguous | 0.3033 | benign | -0.32 | Destabilizing | 0.055 | N | 0.411 | neutral | None | None | None | None | N |
| C/F | 0.2328 | likely_benign | 0.1982 | benign | -0.848 | Destabilizing | 0.427 | N | 0.571 | neutral | N | 0.418874742 | None | None | N |
| C/G | 0.1047 | likely_benign | 0.0738 | benign | -0.656 | Destabilizing | 0.081 | N | 0.451 | neutral | N | 0.310744412 | None | None | N |
| C/H | 0.2105 | likely_benign | 0.1551 | benign | -1.154 | Destabilizing | None | N | 0.179 | neutral | None | None | None | None | N |
| C/I | 0.3119 | likely_benign | 0.2479 | benign | -0.258 | Destabilizing | 0.364 | N | 0.477 | neutral | None | None | None | None | N |
| C/K | 0.2047 | likely_benign | 0.1337 | benign | 0.182 | Stabilizing | None | N | 0.156 | neutral | None | None | None | None | N |
| C/L | 0.2607 | likely_benign | 0.2084 | benign | -0.258 | Destabilizing | 0.104 | N | 0.399 | neutral | None | None | None | None | N |
| C/M | 0.3296 | likely_benign | 0.2733 | benign | 0.126 | Stabilizing | 0.859 | D | 0.439 | neutral | None | None | None | None | N |
| C/N | 0.2295 | likely_benign | 0.1621 | benign | 0.328 | Stabilizing | 0.055 | N | 0.464 | neutral | None | None | None | None | N |
| C/P | 0.4784 | ambiguous | 0.3805 | ambiguous | -0.323 | Destabilizing | 0.364 | N | 0.58 | neutral | None | None | None | None | N |
| C/Q | 0.1812 | likely_benign | 0.1442 | benign | 0.096 | Stabilizing | 0.124 | N | 0.537 | neutral | None | None | None | None | N |
| C/R | 0.1011 | likely_benign | 0.0732 | benign | 0.283 | Stabilizing | 0.042 | N | 0.45 | neutral | N | 0.287907625 | None | None | N |
| C/S | 0.1372 | likely_benign | 0.1009 | benign | 0.096 | Stabilizing | 0.042 | N | 0.367 | neutral | N | 0.292174507 | None | None | N |
| C/T | 0.2269 | likely_benign | 0.1677 | benign | 0.187 | Stabilizing | 0.104 | N | 0.428 | neutral | None | None | None | None | N |
| C/V | 0.253 | likely_benign | 0.2149 | benign | -0.323 | Destabilizing | 0.104 | N | 0.411 | neutral | None | None | None | None | N |
| C/W | 0.3845 | ambiguous | 0.297 | benign | -0.925 | Destabilizing | 0.946 | D | 0.517 | neutral | N | 0.400115623 | None | None | N |
| C/Y | 0.2159 | likely_benign | 0.1703 | benign | -0.657 | Destabilizing | 0.096 | N | 0.551 | neutral | N | 0.399942264 | 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.