Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22063 | 66412;66413;66414 | chr2:178582182;178582181;178582180 | chr2:179446909;179446908;179446907 |
| N2AB | 20422 | 61489;61490;61491 | chr2:178582182;178582181;178582180 | chr2:179446909;179446908;179446907 |
| N2A | 19495 | 58708;58709;58710 | chr2:178582182;178582181;178582180 | chr2:179446909;179446908;179446907 |
| N2B | 12998 | 39217;39218;39219 | chr2:178582182;178582181;178582180 | chr2:179446909;179446908;179446907 |
| Novex-1 | 13123 | 39592;39593;39594 | chr2:178582182;178582181;178582180 | chr2:179446909;179446908;179446907 |
| Novex-2 | 13190 | 39793;39794;39795 | chr2:178582182;178582181;178582180 | chr2:179446909;179446908;179446907 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs768057735  |
-0.192 | 0.489 | N | 0.437 | 0.104 | None | gnomAD-2.1.1 | 6.49E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.43699E-04 | 0 |
| V/L | rs768057735 |
-0.192 | 0.489 | N | 0.437 | 0.104 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.82E-05 | 0 | 0 |
| V/L | rs768057735 |
-0.192 | 0.489 | N | 0.437 | 0.104 | None | gnomAD-4.0.0 | 5.51877E-05 | None | None | None | None | N | None | 1.33629E-05 | 0 | None | 0 | 0 | None | 0 | 1.64962E-04 | 7.20675E-05 | 1.09893E-05 | 1.60205E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2154 | likely_benign | 0.2249 | benign | -0.669 | Destabilizing | 0.822 | D | 0.453 | neutral | N | 0.501471909 | None | None | N |
| V/C | 0.73 | likely_pathogenic | 0.7523 | pathogenic | -0.734 | Destabilizing | 0.998 | D | 0.675 | prob.neutral | None | None | None | None | N |
| V/D | 0.44 | ambiguous | 0.4224 | ambiguous | -0.159 | Destabilizing | 0.89 | D | 0.648 | neutral | N | 0.468063875 | None | None | N |
| V/E | 0.2928 | likely_benign | 0.2925 | benign | -0.247 | Destabilizing | 0.043 | N | 0.477 | neutral | None | None | None | None | N |
| V/F | 0.228 | likely_benign | 0.2324 | benign | -0.721 | Destabilizing | 0.942 | D | 0.681 | prob.neutral | N | 0.517153437 | None | None | N |
| V/G | 0.3367 | likely_benign | 0.3305 | benign | -0.845 | Destabilizing | 0.942 | D | 0.661 | neutral | N | 0.508283238 | None | None | N |
| V/H | 0.5743 | likely_pathogenic | 0.5922 | pathogenic | -0.396 | Destabilizing | 0.994 | D | 0.705 | prob.neutral | None | None | None | None | N |
| V/I | 0.0725 | likely_benign | 0.0769 | benign | -0.343 | Destabilizing | 0.014 | N | 0.273 | neutral | N | 0.450813802 | None | None | N |
| V/K | 0.4538 | ambiguous | 0.4449 | ambiguous | -0.534 | Destabilizing | 0.915 | D | 0.619 | neutral | None | None | None | None | N |
| V/L | 0.1688 | likely_benign | 0.169 | benign | -0.343 | Destabilizing | 0.489 | N | 0.437 | neutral | N | 0.498394318 | None | None | N |
| V/M | 0.1466 | likely_benign | 0.1494 | benign | -0.372 | Destabilizing | 0.956 | D | 0.59 | neutral | None | None | None | None | N |
| V/N | 0.2539 | likely_benign | 0.2656 | benign | -0.312 | Destabilizing | 0.956 | D | 0.709 | prob.delet. | None | None | None | None | N |
| V/P | 0.9291 | likely_pathogenic | 0.9173 | pathogenic | -0.415 | Destabilizing | 0.978 | D | 0.695 | prob.neutral | None | None | None | None | N |
| V/Q | 0.307 | likely_benign | 0.3201 | benign | -0.524 | Destabilizing | 0.915 | D | 0.695 | prob.neutral | None | None | None | None | N |
| V/R | 0.4458 | ambiguous | 0.4237 | ambiguous | -0.056 | Destabilizing | 0.956 | D | 0.711 | prob.delet. | None | None | None | None | N |
| V/S | 0.2358 | likely_benign | 0.2296 | benign | -0.758 | Destabilizing | 0.956 | D | 0.617 | neutral | None | None | None | None | N |
| V/T | 0.196 | likely_benign | 0.2015 | benign | -0.739 | Destabilizing | 0.86 | D | 0.498 | neutral | None | None | None | None | N |
| V/W | 0.8754 | likely_pathogenic | 0.8865 | pathogenic | -0.802 | Destabilizing | 0.998 | D | 0.673 | neutral | None | None | None | None | N |
| V/Y | 0.5616 | ambiguous | 0.5788 | pathogenic | -0.505 | Destabilizing | 0.993 | D | 0.693 | 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.