Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15579 | 46960;46961;46962 | chr2:178618815;178618814;178618813 | chr2:179483542;179483541;179483540 |
| N2AB | 13938 | 42037;42038;42039 | chr2:178618815;178618814;178618813 | chr2:179483542;179483541;179483540 |
| N2A | 13011 | 39256;39257;39258 | chr2:178618815;178618814;178618813 | chr2:179483542;179483541;179483540 |
| N2B | 6514 | 19765;19766;19767 | chr2:178618815;178618814;178618813 | chr2:179483542;179483541;179483540 |
| Novex-1 | 6639 | 20140;20141;20142 | chr2:178618815;178618814;178618813 | chr2:179483542;179483541;179483540 |
| Novex-2 | 6706 | 20341;20342;20343 | chr2:178618815;178618814;178618813 | chr2:179483542;179483541;179483540 |
| 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/A | None | None | 0.78 | N | 0.43 | 0.44 | 0.545389625809 | gnomAD-4.0.0 | 1.37097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.92456E-04 | 9.00293E-07 | 0 | 0 |
| V/I | rs753144532  |
-0.513 | 0.026 | N | 0.215 | 0.193 | 0.414281671643 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.67E-05 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs753144532 |
-0.513 | 0.026 | N | 0.215 | 0.193 | 0.414281671643 | gnomAD-4.0.0 | 1.59837E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.79517E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.239 | likely_benign | 0.3328 | benign | -1.584 | Destabilizing | 0.78 | D | 0.43 | neutral | N | 0.518933814 | None | None | N |
| V/C | 0.768 | likely_pathogenic | 0.8238 | pathogenic | -1.092 | Destabilizing | 0.999 | D | 0.534 | neutral | None | None | None | None | N |
| V/D | 0.8814 | likely_pathogenic | 0.9208 | pathogenic | -1.44 | Destabilizing | 0.984 | D | 0.581 | neutral | D | 0.528025689 | None | None | N |
| V/E | 0.7901 | likely_pathogenic | 0.8382 | pathogenic | -1.373 | Destabilizing | 0.988 | D | 0.523 | neutral | None | None | None | None | N |
| V/F | 0.3924 | ambiguous | 0.5064 | ambiguous | -1.036 | Destabilizing | 0.968 | D | 0.559 | neutral | D | 0.526657848 | None | None | N |
| V/G | 0.4975 | ambiguous | 0.5907 | pathogenic | -1.978 | Destabilizing | 0.984 | D | 0.554 | neutral | D | 0.527437478 | None | None | N |
| V/H | 0.9212 | likely_pathogenic | 0.9453 | pathogenic | -1.565 | Destabilizing | 0.999 | D | 0.572 | neutral | None | None | None | None | N |
| V/I | 0.0882 | likely_benign | 0.1117 | benign | -0.573 | Destabilizing | 0.026 | N | 0.215 | neutral | N | 0.48379679 | None | None | N |
| V/K | 0.8478 | likely_pathogenic | 0.8816 | pathogenic | -1.366 | Destabilizing | 0.976 | D | 0.521 | neutral | None | None | None | None | N |
| V/L | 0.3022 | likely_benign | 0.4191 | ambiguous | -0.573 | Destabilizing | 0.64 | D | 0.405 | neutral | D | 0.522904603 | None | None | N |
| V/M | 0.2298 | likely_benign | 0.3442 | ambiguous | -0.482 | Destabilizing | 0.976 | D | 0.527 | neutral | None | None | None | None | N |
| V/N | 0.7626 | likely_pathogenic | 0.829 | pathogenic | -1.276 | Destabilizing | 0.988 | D | 0.587 | neutral | None | None | None | None | N |
| V/P | 0.9708 | likely_pathogenic | 0.983 | pathogenic | -0.876 | Destabilizing | 0.996 | D | 0.545 | neutral | None | None | None | None | N |
| V/Q | 0.781 | likely_pathogenic | 0.8232 | pathogenic | -1.336 | Destabilizing | 0.996 | D | 0.563 | neutral | None | None | None | None | N |
| V/R | 0.8095 | likely_pathogenic | 0.8362 | pathogenic | -0.963 | Destabilizing | 0.988 | D | 0.603 | neutral | None | None | None | None | N |
| V/S | 0.4741 | ambiguous | 0.572 | pathogenic | -1.866 | Destabilizing | 0.851 | D | 0.49 | neutral | None | None | None | None | N |
| V/T | 0.1966 | likely_benign | 0.2542 | benign | -1.678 | Destabilizing | 0.06 | N | 0.171 | neutral | None | None | None | None | N |
| V/W | 0.9546 | likely_pathogenic | 0.972 | pathogenic | -1.335 | Destabilizing | 0.999 | D | 0.587 | neutral | None | None | None | None | N |
| V/Y | 0.8516 | likely_pathogenic | 0.8979 | pathogenic | -1.003 | Destabilizing | 0.996 | D | 0.558 | 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.