Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32105 | 96538;96539;96540 | chr2:178543660;178543659;178543658 | chr2:179408387;179408386;179408385 |
| N2AB | 30464 | 91615;91616;91617 | chr2:178543660;178543659;178543658 | chr2:179408387;179408386;179408385 |
| N2A | 29537 | 88834;88835;88836 | chr2:178543660;178543659;178543658 | chr2:179408387;179408386;179408385 |
| N2B | 23040 | 69343;69344;69345 | chr2:178543660;178543659;178543658 | chr2:179408387;179408386;179408385 |
| Novex-1 | 23165 | 69718;69719;69720 | chr2:178543660;178543659;178543658 | chr2:179408387;179408386;179408385 |
| Novex-2 | 23232 | 69919;69920;69921 | chr2:178543660;178543659;178543658 | chr2:179408387;179408386;179408385 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs768124637  |
-0.554 | 0.995 | N | 0.713 | 0.29 | 0.336400405673 | gnomAD-4.0.0 | 2.10096E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 2.41511E-05 | 0 | 9.08797E-07 | 1.20322E-05 | 0 |
| T/S | rs768124637 |
None | 0.027 | N | 0.276 | 0.062 | 0.16115917748 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/S | rs768124637 |
None | 0.027 | N | 0.276 | 0.062 | 0.16115917748 | gnomAD-4.0.0 | 1.26578E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.71177E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2337 | likely_benign | 0.1985 | benign | -0.843 | Destabilizing | 0.303 | N | 0.441 | neutral | N | 0.488240748 | None | None | I |
| T/C | 0.6967 | likely_pathogenic | 0.6735 | pathogenic | -0.494 | Destabilizing | 1.0 | D | 0.702 | prob.delet. | None | None | None | None | I |
| T/D | 0.9312 | likely_pathogenic | 0.9074 | pathogenic | -0.064 | Destabilizing | 0.968 | D | 0.672 | prob.neutral | None | None | None | None | I |
| T/E | 0.881 | likely_pathogenic | 0.8367 | pathogenic | -0.119 | Destabilizing | 0.99 | D | 0.683 | prob.neutral | None | None | None | None | I |
| T/F | 0.8201 | likely_pathogenic | 0.7514 | pathogenic | -1.23 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | I |
| T/G | 0.6289 | likely_pathogenic | 0.5783 | pathogenic | -1.002 | Destabilizing | 0.973 | D | 0.651 | prob.neutral | None | None | None | None | I |
| T/H | 0.7534 | likely_pathogenic | 0.6832 | pathogenic | -1.354 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| T/I | 0.5818 | likely_pathogenic | 0.5099 | ambiguous | -0.524 | Destabilizing | 0.995 | D | 0.713 | prob.delet. | N | 0.512619117 | None | None | I |
| T/K | 0.7541 | likely_pathogenic | 0.6419 | pathogenic | -0.553 | Destabilizing | 0.993 | D | 0.672 | prob.neutral | None | None | None | None | I |
| T/L | 0.4401 | ambiguous | 0.3421 | ambiguous | -0.524 | Destabilizing | 0.976 | D | 0.652 | prob.neutral | None | None | None | None | I |
| T/M | 0.2647 | likely_benign | 0.2117 | benign | -0.077 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | I |
| T/N | 0.5235 | ambiguous | 0.4403 | ambiguous | -0.369 | Destabilizing | 0.958 | D | 0.649 | prob.neutral | N | 0.489494314 | None | None | I |
| T/P | 0.5113 | ambiguous | 0.4059 | ambiguous | -0.602 | Destabilizing | 0.979 | D | 0.728 | deleterious | N | 0.497300161 | None | None | I |
| T/Q | 0.7239 | likely_pathogenic | 0.6357 | pathogenic | -0.69 | Destabilizing | 0.993 | D | 0.715 | prob.delet. | None | None | None | None | I |
| T/R | 0.7437 | likely_pathogenic | 0.6353 | pathogenic | -0.253 | Destabilizing | 0.997 | D | 0.711 | prob.delet. | None | None | None | None | I |
| T/S | 0.1629 | likely_benign | 0.1542 | benign | -0.67 | Destabilizing | 0.027 | N | 0.276 | neutral | N | 0.467174829 | None | None | I |
| T/V | 0.3924 | ambiguous | 0.3298 | benign | -0.602 | Destabilizing | 0.966 | D | 0.59 | neutral | None | None | None | None | I |
| T/W | 0.9634 | likely_pathogenic | 0.9505 | pathogenic | -1.103 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| T/Y | 0.8134 | likely_pathogenic | 0.75 | pathogenic | -0.87 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
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.