Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21432 | 64519;64520;64521 | chr2:178586607;178586606;178586605 | chr2:179451334;179451333;179451332 |
| N2AB | 19791 | 59596;59597;59598 | chr2:178586607;178586606;178586605 | chr2:179451334;179451333;179451332 |
| N2A | 18864 | 56815;56816;56817 | chr2:178586607;178586606;178586605 | chr2:179451334;179451333;179451332 |
| N2B | 12367 | 37324;37325;37326 | chr2:178586607;178586606;178586605 | chr2:179451334;179451333;179451332 |
| Novex-1 | 12492 | 37699;37700;37701 | chr2:178586607;178586606;178586605 | chr2:179451334;179451333;179451332 |
| Novex-2 | 12559 | 37900;37901;37902 | chr2:178586607;178586606;178586605 | chr2:179451334;179451333;179451332 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/R | rs1297397587  |
-0.02 | 0.998 | N | 0.505 | 0.255 | 0.47558534428 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| K/R | rs1297397587 |
-0.02 | 0.998 | N | 0.505 | 0.255 | 0.47558534428 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| K/R | rs1297397587 |
-0.02 | 0.998 | N | 0.505 | 0.255 | 0.47558534428 | gnomAD-4.0.0 | 7.43908E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32657E-06 | 0 | 1.602E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.4533 | ambiguous | 0.3761 | ambiguous | -0.455 | Destabilizing | 0.998 | D | 0.581 | neutral | None | None | None | None | N |
| K/C | 0.7664 | likely_pathogenic | 0.6974 | pathogenic | -0.614 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| K/D | 0.7879 | likely_pathogenic | 0.7197 | pathogenic | -0.165 | Destabilizing | 0.998 | D | 0.579 | neutral | None | None | None | None | N |
| K/E | 0.2768 | likely_benign | 0.2135 | benign | -0.068 | Destabilizing | 0.996 | D | 0.472 | neutral | N | 0.480731277 | None | None | N |
| K/F | 0.8882 | likely_pathogenic | 0.8405 | pathogenic | -0.327 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| K/G | 0.6614 | likely_pathogenic | 0.5803 | pathogenic | -0.754 | Destabilizing | 0.997 | D | 0.519 | neutral | None | None | None | None | N |
| K/H | 0.3955 | ambiguous | 0.3498 | ambiguous | -0.87 | Destabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | N |
| K/I | 0.4528 | ambiguous | 0.3611 | ambiguous | 0.297 | Stabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| K/L | 0.4636 | ambiguous | 0.3768 | ambiguous | 0.297 | Stabilizing | 1.0 | D | 0.523 | neutral | None | None | None | None | N |
| K/M | 0.3557 | ambiguous | 0.2755 | benign | -0.098 | Destabilizing | 1.0 | D | 0.649 | neutral | D | 0.523543479 | None | None | N |
| K/N | 0.6579 | likely_pathogenic | 0.5693 | pathogenic | -0.414 | Destabilizing | 0.884 | D | 0.313 | neutral | N | 0.482003501 | None | None | N |
| K/P | 0.8403 | likely_pathogenic | 0.821 | pathogenic | 0.074 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| K/Q | 0.1512 | likely_benign | 0.1299 | benign | -0.413 | Destabilizing | 0.999 | D | 0.649 | neutral | N | 0.460492078 | None | None | N |
| K/R | 0.0882 | likely_benign | 0.0867 | benign | -0.365 | Destabilizing | 0.998 | D | 0.505 | neutral | N | 0.492583067 | None | None | N |
| K/S | 0.5923 | likely_pathogenic | 0.4965 | ambiguous | -0.94 | Destabilizing | 0.997 | D | 0.51 | neutral | None | None | None | None | N |
| K/T | 0.2417 | likely_benign | 0.1941 | benign | -0.649 | Destabilizing | 0.999 | D | 0.58 | neutral | N | 0.466244614 | None | None | N |
| K/V | 0.3657 | ambiguous | 0.2956 | benign | 0.074 | Stabilizing | 1.0 | D | 0.614 | neutral | None | None | None | None | N |
| K/W | 0.8464 | likely_pathogenic | 0.7955 | pathogenic | -0.31 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| K/Y | 0.7879 | likely_pathogenic | 0.7316 | pathogenic | -0.009 | Destabilizing | 1.0 | D | 0.637 | 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.