Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31599 | 95020;95021;95022 | chr2:178546633;178546632;178546631 | chr2:179411360;179411359;179411358 |
| N2AB | 29958 | 90097;90098;90099 | chr2:178546633;178546632;178546631 | chr2:179411360;179411359;179411358 |
| N2A | 29031 | 87316;87317;87318 | chr2:178546633;178546632;178546631 | chr2:179411360;179411359;179411358 |
| N2B | 22534 | 67825;67826;67827 | chr2:178546633;178546632;178546631 | chr2:179411360;179411359;179411358 |
| Novex-1 | 22659 | 68200;68201;68202 | chr2:178546633;178546632;178546631 | chr2:179411360;179411359;179411358 |
| Novex-2 | 22726 | 68401;68402;68403 | chr2:178546633;178546632;178546631 | chr2:179411360;179411359;179411358 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs1456653211  |
-0.873 | 0.999 | N | 0.508 | 0.34 | 0.350746614512 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.665E-04 |
| S/C | rs1456653211 |
-0.873 | 0.999 | N | 0.508 | 0.34 | 0.350746614512 | gnomAD-4.0.0 | 1.59396E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.0281E-05 |
| S/F | rs1456653211 |
None | 0.987 | N | 0.672 | 0.381 | 0.491387584038 | gnomAD-4.0.0 | 1.59396E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86502E-06 | 0 | 0 |
| S/T | rs376588396 |
-0.759 | 0.126 | N | 0.405 | 0.079 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1168 | likely_benign | 0.1215 | benign | -0.978 | Destabilizing | 0.817 | D | 0.473 | neutral | N | 0.49200149 | None | None | N |
| S/C | 0.178 | likely_benign | 0.1655 | benign | -0.679 | Destabilizing | 0.999 | D | 0.508 | neutral | N | 0.471605366 | None | None | N |
| S/D | 0.7652 | likely_pathogenic | 0.7237 | pathogenic | -0.405 | Destabilizing | 0.967 | D | 0.445 | neutral | None | None | None | None | N |
| S/E | 0.8329 | likely_pathogenic | 0.804 | pathogenic | -0.378 | Destabilizing | 0.967 | D | 0.461 | neutral | None | None | None | None | N |
| S/F | 0.6384 | likely_pathogenic | 0.597 | pathogenic | -1.046 | Destabilizing | 0.987 | D | 0.672 | prob.neutral | N | 0.488820568 | None | None | N |
| S/G | 0.1524 | likely_benign | 0.151 | benign | -1.249 | Destabilizing | 0.967 | D | 0.475 | neutral | None | None | None | None | N |
| S/H | 0.73 | likely_pathogenic | 0.6894 | pathogenic | -1.586 | Destabilizing | 0.999 | D | 0.505 | neutral | None | None | None | None | N |
| S/I | 0.341 | ambiguous | 0.3189 | benign | -0.35 | Destabilizing | 0.877 | D | 0.547 | neutral | None | None | None | None | N |
| S/K | 0.9282 | likely_pathogenic | 0.9087 | pathogenic | -0.681 | Destabilizing | 0.967 | D | 0.456 | neutral | None | None | None | None | N |
| S/L | 0.2476 | likely_benign | 0.2357 | benign | -0.35 | Destabilizing | 0.877 | D | 0.59 | neutral | None | None | None | None | N |
| S/M | 0.3732 | ambiguous | 0.3564 | ambiguous | -0.084 | Destabilizing | 0.99 | D | 0.499 | neutral | None | None | None | None | N |
| S/N | 0.2929 | likely_benign | 0.2602 | benign | -0.71 | Destabilizing | 0.967 | D | 0.494 | neutral | None | None | None | None | N |
| S/P | 0.1507 | likely_benign | 0.1484 | benign | -0.527 | Destabilizing | 0.033 | N | 0.444 | neutral | N | 0.459944999 | None | None | N |
| S/Q | 0.8166 | likely_pathogenic | 0.7864 | pathogenic | -0.86 | Destabilizing | 0.997 | D | 0.439 | neutral | None | None | None | None | N |
| S/R | 0.9136 | likely_pathogenic | 0.8925 | pathogenic | -0.582 | Destabilizing | 0.99 | D | 0.452 | neutral | None | None | None | None | N |
| S/T | 0.1069 | likely_benign | 0.1077 | benign | -0.747 | Destabilizing | 0.126 | N | 0.405 | neutral | N | 0.472205008 | None | None | N |
| S/V | 0.3001 | likely_benign | 0.2898 | benign | -0.527 | Destabilizing | 0.161 | N | 0.567 | neutral | None | None | None | None | N |
| S/W | 0.751 | likely_pathogenic | 0.7112 | pathogenic | -0.97 | Destabilizing | 0.999 | D | 0.781 | deleterious | None | None | None | None | N |
| S/Y | 0.5772 | likely_pathogenic | 0.5084 | ambiguous | -0.718 | Destabilizing | 0.996 | D | 0.667 | prob.neutral | N | 0.496328986 | 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.