Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17660 | 53203;53204;53205 | chr2:178607809;178607808;178607807 | chr2:179472536;179472535;179472534 |
| N2AB | 16019 | 48280;48281;48282 | chr2:178607809;178607808;178607807 | chr2:179472536;179472535;179472534 |
| N2A | 15092 | 45499;45500;45501 | chr2:178607809;178607808;178607807 | chr2:179472536;179472535;179472534 |
| N2B | 8595 | 26008;26009;26010 | chr2:178607809;178607808;178607807 | chr2:179472536;179472535;179472534 |
| Novex-1 | 8720 | 26383;26384;26385 | chr2:178607809;178607808;178607807 | chr2:179472536;179472535;179472534 |
| Novex-2 | 8787 | 26584;26585;26586 | chr2:178607809;178607808;178607807 | chr2:179472536;179472535;179472534 |
| 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 | None | None | 0.842 | N | 0.629 | 0.351 | 0.329540904979 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| P/S | rs957490512  |
-0.498 | 0.08 | N | 0.225 | 0.19 | 0.151104730317 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| P/S | rs957490512 |
-0.498 | 0.08 | N | 0.225 | 0.19 | 0.151104730317 | gnomAD-4.0.0 | 1.59297E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86134E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0688 | likely_benign | 0.0697 | benign | -0.722 | Destabilizing | 0.029 | N | 0.235 | neutral | N | 0.438910792 | None | None | N |
| P/C | 0.5353 | ambiguous | 0.5358 | ambiguous | -0.564 | Destabilizing | 0.998 | D | 0.681 | prob.neutral | None | None | None | None | N |
| P/D | 0.4754 | ambiguous | 0.4925 | ambiguous | -0.531 | Destabilizing | 0.876 | D | 0.522 | neutral | None | None | None | None | N |
| P/E | 0.3246 | likely_benign | 0.3339 | benign | -0.639 | Destabilizing | 0.876 | D | 0.462 | neutral | None | None | None | None | N |
| P/F | 0.5504 | ambiguous | 0.528 | ambiguous | -0.866 | Destabilizing | 0.994 | D | 0.683 | prob.neutral | None | None | None | None | N |
| P/G | 0.361 | ambiguous | 0.3639 | ambiguous | -0.894 | Destabilizing | 0.594 | D | 0.53 | neutral | None | None | None | None | N |
| P/H | 0.3035 | likely_benign | 0.3039 | benign | -0.461 | Destabilizing | 0.998 | D | 0.623 | neutral | N | 0.461021259 | None | None | N |
| P/I | 0.2751 | likely_benign | 0.2917 | benign | -0.407 | Destabilizing | 0.961 | D | 0.71 | prob.delet. | None | None | None | None | N |
| P/K | 0.411 | ambiguous | 0.4301 | ambiguous | -0.607 | Destabilizing | 0.876 | D | 0.46 | neutral | None | None | None | None | N |
| P/L | 0.1276 | likely_benign | 0.1253 | benign | -0.407 | Destabilizing | 0.842 | D | 0.629 | neutral | N | 0.500439254 | None | None | N |
| P/M | 0.3173 | likely_benign | 0.3184 | benign | -0.301 | Destabilizing | 0.998 | D | 0.625 | neutral | None | None | None | None | N |
| P/N | 0.3935 | ambiguous | 0.4002 | ambiguous | -0.254 | Destabilizing | 0.876 | D | 0.624 | neutral | None | None | None | None | N |
| P/Q | 0.2515 | likely_benign | 0.2504 | benign | -0.534 | Destabilizing | 0.981 | D | 0.581 | neutral | None | None | None | None | N |
| P/R | 0.2823 | likely_benign | 0.2844 | benign | -0.032 | Destabilizing | 0.974 | D | 0.659 | prob.neutral | N | 0.46026079 | None | None | N |
| P/S | 0.1545 | likely_benign | 0.1532 | benign | -0.641 | Destabilizing | 0.08 | N | 0.225 | neutral | N | 0.455360325 | None | None | N |
| P/T | 0.1122 | likely_benign | 0.1121 | benign | -0.65 | Destabilizing | 0.067 | N | 0.26 | neutral | N | 0.467673474 | None | None | N |
| P/V | 0.1761 | likely_benign | 0.1843 | benign | -0.476 | Destabilizing | 0.876 | D | 0.583 | neutral | None | None | None | None | N |
| P/W | 0.6913 | likely_pathogenic | 0.6692 | pathogenic | -0.941 | Destabilizing | 0.998 | D | 0.721 | deleterious | None | None | None | None | N |
| P/Y | 0.5002 | ambiguous | 0.499 | ambiguous | -0.653 | Destabilizing | 0.994 | D | 0.681 | prob.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.