Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28944 | 87055;87056;87057 | chr2:178558629;178558628;178558627 | chr2:179423356;179423355;179423354 |
| N2AB | 27303 | 82132;82133;82134 | chr2:178558629;178558628;178558627 | chr2:179423356;179423355;179423354 |
| N2A | 26376 | 79351;79352;79353 | chr2:178558629;178558628;178558627 | chr2:179423356;179423355;179423354 |
| N2B | 19879 | 59860;59861;59862 | chr2:178558629;178558628;178558627 | chr2:179423356;179423355;179423354 |
| Novex-1 | 20004 | 60235;60236;60237 | chr2:178558629;178558628;178558627 | chr2:179423356;179423355;179423354 |
| Novex-2 | 20071 | 60436;60437;60438 | chr2:178558629;178558628;178558627 | chr2:179423356;179423355;179423354 |
| 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 | None | None | 1.0 | N | 0.685 | 0.514 | 0.514015564596 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| S/R | rs550405800  |
-0.516 | 0.999 | N | 0.688 | 0.472 | 0.340753184043 | gnomAD-2.1.1 | 4.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.38E-05 | None | 0 | 0 | 0 |
| S/R | rs550405800 |
-0.516 | 0.999 | N | 0.688 | 0.472 | 0.340753184043 | gnomAD-4.0.0 | 1.5996E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4551E-05 | 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 | 0.0879 | likely_benign | 0.0855 | benign | -0.424 | Destabilizing | 0.98 | D | 0.541 | neutral | None | None | None | None | N |
| S/C | 0.1388 | likely_benign | 0.1362 | benign | -0.513 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.516614012 | None | None | N |
| S/D | 0.6534 | likely_pathogenic | 0.7096 | pathogenic | -1.471 | Destabilizing | 0.996 | D | 0.635 | neutral | None | None | None | None | N |
| S/E | 0.7644 | likely_pathogenic | 0.7827 | pathogenic | -1.426 | Destabilizing | 0.999 | D | 0.637 | neutral | None | None | None | None | N |
| S/F | 0.2467 | likely_benign | 0.2444 | benign | -0.497 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| S/G | 0.0951 | likely_benign | 0.0989 | benign | -0.71 | Destabilizing | 0.104 | N | 0.352 | neutral | N | 0.447432354 | None | None | N |
| S/H | 0.5701 | likely_pathogenic | 0.6001 | pathogenic | -1.317 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| S/I | 0.4047 | ambiguous | 0.3913 | ambiguous | 0.241 | Stabilizing | 0.999 | D | 0.781 | deleterious | N | 0.516360522 | None | None | N |
| S/K | 0.8622 | likely_pathogenic | 0.8681 | pathogenic | -0.855 | Destabilizing | 0.996 | D | 0.642 | neutral | None | None | None | None | N |
| S/L | 0.0821 | likely_benign | 0.0749 | benign | 0.241 | Stabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| S/M | 0.2233 | likely_benign | 0.2123 | benign | 0.486 | Stabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| S/N | 0.2941 | likely_benign | 0.318 | benign | -1.119 | Destabilizing | 0.994 | D | 0.627 | neutral | N | 0.482999168 | None | None | N |
| S/P | 0.8645 | likely_pathogenic | 0.8608 | pathogenic | 0.055 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| S/Q | 0.6759 | likely_pathogenic | 0.6777 | pathogenic | -1.214 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| S/R | 0.838 | likely_pathogenic | 0.8507 | pathogenic | -0.812 | Destabilizing | 0.999 | D | 0.688 | prob.neutral | N | 0.497242309 | None | None | N |
| S/T | 0.139 | likely_benign | 0.1359 | benign | -0.858 | Destabilizing | 0.994 | D | 0.574 | neutral | D | 0.527221289 | None | None | N |
| S/V | 0.3309 | likely_benign | 0.3208 | benign | 0.055 | Stabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| S/W | 0.4909 | ambiguous | 0.5011 | ambiguous | -0.672 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| S/Y | 0.256 | likely_benign | 0.2725 | benign | -0.318 | Destabilizing | 1.0 | D | 0.799 | deleterious | 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.