Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31522 | 94789;94790;94791 | chr2:178546864;178546863;178546862 | chr2:179411591;179411590;179411589 |
| N2AB | 29881 | 89866;89867;89868 | chr2:178546864;178546863;178546862 | chr2:179411591;179411590;179411589 |
| N2A | 28954 | 87085;87086;87087 | chr2:178546864;178546863;178546862 | chr2:179411591;179411590;179411589 |
| N2B | 22457 | 67594;67595;67596 | chr2:178546864;178546863;178546862 | chr2:179411591;179411590;179411589 |
| Novex-1 | 22582 | 67969;67970;67971 | chr2:178546864;178546863;178546862 | chr2:179411591;179411590;179411589 |
| Novex-2 | 22649 | 68170;68171;68172 | chr2:178546864;178546863;178546862 | chr2:179411591;179411590;179411589 |
| 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/A | rs1697400184  |
None | 0.64 | N | 0.401 | 0.12 | 0.258283824007 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| T/I | rs1360429703 |
-0.093 | 0.984 | N | 0.687 | 0.466 | 0.527759996296 | gnomAD-2.1.1 | 4.16E-06 | None | None | None | None | N | None | 0 | 2.95E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs1360429703 |
-0.093 | 0.984 | N | 0.687 | 0.466 | 0.527759996296 | gnomAD-4.0.0 | 1.6296E-06 | None | None | None | None | N | None | 0 | 2.31289E-05 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1205 | likely_benign | 0.1137 | benign | -0.674 | Destabilizing | 0.64 | D | 0.401 | neutral | N | 0.460204076 | None | None | N |
| T/C | 0.5344 | ambiguous | 0.4873 | ambiguous | -0.87 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | N |
| T/D | 0.8199 | likely_pathogenic | 0.7763 | pathogenic | -1.58 | Destabilizing | 0.919 | D | 0.629 | neutral | None | None | None | None | N |
| T/E | 0.7258 | likely_pathogenic | 0.6884 | pathogenic | -1.546 | Destabilizing | 0.919 | D | 0.622 | neutral | None | None | None | None | N |
| T/F | 0.5765 | likely_pathogenic | 0.5154 | ambiguous | -0.979 | Destabilizing | 0.996 | D | 0.749 | deleterious | None | None | None | None | N |
| T/G | 0.3661 | ambiguous | 0.3054 | benign | -0.913 | Destabilizing | 0.851 | D | 0.601 | neutral | None | None | None | None | N |
| T/H | 0.5057 | ambiguous | 0.4526 | ambiguous | -1.312 | Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | N |
| T/I | 0.7488 | likely_pathogenic | 0.7354 | pathogenic | -0.125 | Destabilizing | 0.984 | D | 0.687 | prob.neutral | N | 0.483716276 | None | None | N |
| T/K | 0.6635 | likely_pathogenic | 0.6365 | pathogenic | -0.694 | Destabilizing | 0.896 | D | 0.623 | neutral | D | 0.524772843 | None | None | N |
| T/L | 0.3718 | ambiguous | 0.344 | ambiguous | -0.125 | Destabilizing | 0.919 | D | 0.596 | neutral | None | None | None | None | N |
| T/M | 0.1685 | likely_benign | 0.1588 | benign | 0.154 | Stabilizing | 0.999 | D | 0.708 | prob.delet. | None | None | None | None | N |
| T/N | 0.318 | likely_benign | 0.2809 | benign | -1.027 | Destabilizing | 0.919 | D | 0.521 | neutral | None | None | None | None | N |
| T/P | 0.9684 | likely_pathogenic | 0.9583 | pathogenic | -0.278 | Destabilizing | 0.984 | D | 0.688 | prob.neutral | N | 0.495072581 | None | None | N |
| T/Q | 0.4838 | ambiguous | 0.4631 | ambiguous | -1.278 | Destabilizing | 0.988 | D | 0.699 | prob.neutral | None | None | None | None | N |
| T/R | 0.5845 | likely_pathogenic | 0.5633 | ambiguous | -0.445 | Destabilizing | 0.968 | D | 0.697 | prob.neutral | N | 0.506707157 | None | None | N |
| T/S | 0.093 | likely_benign | 0.0789 | benign | -1.087 | Destabilizing | 0.046 | N | 0.212 | neutral | N | 0.356127198 | None | None | N |
| T/V | 0.4789 | ambiguous | 0.471 | ambiguous | -0.278 | Destabilizing | 0.919 | D | 0.503 | neutral | None | None | None | None | N |
| T/W | 0.8779 | likely_pathogenic | 0.837 | pathogenic | -1.033 | Destabilizing | 0.999 | D | 0.765 | deleterious | None | None | None | None | N |
| T/Y | 0.6268 | likely_pathogenic | 0.5558 | ambiguous | -0.656 | Destabilizing | 0.996 | D | 0.761 | 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.