Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21491 | 64696;64697;64698 | chr2:178585273;178585272;178585271 | chr2:179450000;179449999;179449998 |
| N2AB | 19850 | 59773;59774;59775 | chr2:178585273;178585272;178585271 | chr2:179450000;179449999;179449998 |
| N2A | 18923 | 56992;56993;56994 | chr2:178585273;178585272;178585271 | chr2:179450000;179449999;179449998 |
| N2B | 12426 | 37501;37502;37503 | chr2:178585273;178585272;178585271 | chr2:179450000;179449999;179449998 |
| Novex-1 | 12551 | 37876;37877;37878 | chr2:178585273;178585272;178585271 | chr2:179450000;179449999;179449998 |
| Novex-2 | 12618 | 38077;38078;38079 | chr2:178585273;178585272;178585271 | chr2:179450000;179449999;179449998 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs757450750  |
-0.054 | 0.999 | N | 0.343 | 0.296 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 0 | 1.98278E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.40607E-04 |
| Y/C | rs757450750 |
-0.054 | 0.999 | N | 0.343 | 0.296 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Y/C | rs757450750 |
-0.054 | 0.999 | N | 0.343 | 0.296 | None | gnomAD-4.0.0 | 1.2821E-05 | None | None | None | None | N | None | 0 | 1.35658E-04 | None | 0 | 0 | None | 0 | 0 | 4.79044E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.4343 | ambiguous | 0.3331 | benign | -1.512 | Destabilizing | 0.079 | N | 0.201 | neutral | None | None | None | None | N |
| Y/C | 0.1776 | likely_benign | 0.1416 | benign | -0.506 | Destabilizing | 0.999 | D | 0.343 | neutral | N | 0.483188084 | None | None | N |
| Y/D | 0.4231 | ambiguous | 0.3192 | benign | 0.333 | Stabilizing | 0.92 | D | 0.365 | neutral | N | 0.415981657 | None | None | N |
| Y/E | 0.6405 | likely_pathogenic | 0.5455 | ambiguous | 0.386 | Stabilizing | 0.939 | D | 0.351 | neutral | None | None | None | None | N |
| Y/F | 0.0917 | likely_benign | 0.0793 | benign | -0.494 | Destabilizing | 0.986 | D | 0.336 | neutral | N | 0.432201903 | None | None | N |
| Y/G | 0.4835 | ambiguous | 0.3951 | ambiguous | -1.787 | Destabilizing | 0.863 | D | 0.351 | neutral | None | None | None | None | N |
| Y/H | 0.1947 | likely_benign | 0.1529 | benign | -0.287 | Destabilizing | 0.996 | D | 0.421 | neutral | N | 0.448902152 | None | None | N |
| Y/I | 0.3773 | ambiguous | 0.3068 | benign | -0.73 | Destabilizing | 0.969 | D | 0.34 | neutral | None | None | None | None | N |
| Y/K | 0.5768 | likely_pathogenic | 0.4914 | ambiguous | -0.59 | Destabilizing | 0.939 | D | 0.377 | neutral | None | None | None | None | N |
| Y/L | 0.3829 | ambiguous | 0.3393 | benign | -0.73 | Destabilizing | 0.863 | D | 0.291 | neutral | None | None | None | None | N |
| Y/M | 0.5019 | ambiguous | 0.4381 | ambiguous | -0.552 | Destabilizing | 0.997 | D | 0.345 | neutral | None | None | None | None | N |
| Y/N | 0.2336 | likely_benign | 0.1736 | benign | -0.9 | Destabilizing | 0.976 | D | 0.347 | neutral | N | 0.438954517 | None | None | N |
| Y/P | 0.9546 | likely_pathogenic | 0.9325 | pathogenic | -0.979 | Destabilizing | 0.991 | D | 0.351 | neutral | None | None | None | None | N |
| Y/Q | 0.4615 | ambiguous | 0.3655 | ambiguous | -0.783 | Destabilizing | 0.991 | D | 0.352 | neutral | None | None | None | None | N |
| Y/R | 0.3969 | ambiguous | 0.3218 | benign | -0.257 | Destabilizing | 0.991 | D | 0.345 | neutral | None | None | None | None | N |
| Y/S | 0.1808 | likely_benign | 0.1346 | benign | -1.436 | Destabilizing | 0.31 | N | 0.234 | neutral | N | 0.341963901 | None | None | N |
| Y/T | 0.3098 | likely_benign | 0.2374 | benign | -1.29 | Destabilizing | 0.884 | D | 0.328 | neutral | None | None | None | None | N |
| Y/V | 0.3216 | likely_benign | 0.2648 | benign | -0.979 | Destabilizing | 0.939 | D | 0.289 | neutral | None | None | None | None | N |
| Y/W | 0.393 | ambiguous | 0.3382 | benign | -0.279 | Destabilizing | 0.999 | D | 0.418 | 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.