Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25204 | 75835;75836;75837 | chr2:178570522;178570521;178570520 | chr2:179435249;179435248;179435247 |
| N2AB | 23563 | 70912;70913;70914 | chr2:178570522;178570521;178570520 | chr2:179435249;179435248;179435247 |
| N2A | 22636 | 68131;68132;68133 | chr2:178570522;178570521;178570520 | chr2:179435249;179435248;179435247 |
| N2B | 16139 | 48640;48641;48642 | chr2:178570522;178570521;178570520 | chr2:179435249;179435248;179435247 |
| Novex-1 | 16264 | 49015;49016;49017 | chr2:178570522;178570521;178570520 | chr2:179435249;179435248;179435247 |
| Novex-2 | 16331 | 49216;49217;49218 | chr2:178570522;178570521;178570520 | chr2:179435249;179435248;179435247 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 0.321 | N | 0.579 | 0.253 | 0.321108458156 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| R/K | rs1420513249  |
-0.092 | 0.001 | N | 0.242 | 0.057 | 0.144782658237 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/S | rs1707795388 |
None | 0.191 | N | 0.667 | 0.11 | 0.136095386433 | 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 |
| R/S | rs1707795388 |
None | 0.191 | N | 0.667 | 0.11 | 0.136095386433 | gnomAD-4.0.0 | 6.57358E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47085E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.74 | likely_pathogenic | 0.6995 | pathogenic | -0.177 | Destabilizing | 0.239 | N | 0.609 | neutral | None | None | None | None | I |
| R/C | 0.2594 | likely_benign | 0.2333 | benign | -0.359 | Destabilizing | 0.981 | D | 0.869 | deleterious | None | None | None | None | I |
| R/D | 0.9647 | likely_pathogenic | 0.9622 | pathogenic | -0.132 | Destabilizing | 0.687 | D | 0.639 | neutral | None | None | None | None | I |
| R/E | 0.7742 | likely_pathogenic | 0.7469 | pathogenic | -0.06 | Destabilizing | 0.239 | N | 0.578 | neutral | None | None | None | None | I |
| R/F | 0.838 | likely_pathogenic | 0.8195 | pathogenic | -0.335 | Destabilizing | 0.931 | D | 0.818 | deleterious | None | None | None | None | I |
| R/G | 0.7297 | likely_pathogenic | 0.6819 | pathogenic | -0.389 | Destabilizing | 0.321 | N | 0.579 | neutral | N | 0.491255514 | None | None | I |
| R/H | 0.2552 | likely_benign | 0.2229 | benign | -0.779 | Destabilizing | 0.817 | D | 0.629 | neutral | None | None | None | None | I |
| R/I | 0.3784 | ambiguous | 0.3379 | benign | 0.353 | Stabilizing | 0.771 | D | 0.847 | deleterious | N | 0.514563344 | None | None | I |
| R/K | 0.1451 | likely_benign | 0.1299 | benign | -0.307 | Destabilizing | 0.001 | N | 0.242 | neutral | N | 0.414687138 | None | None | I |
| R/L | 0.4991 | ambiguous | 0.4584 | ambiguous | 0.353 | Stabilizing | 0.385 | N | 0.579 | neutral | None | None | None | None | I |
| R/M | 0.5471 | ambiguous | 0.4994 | ambiguous | -0.063 | Destabilizing | 0.981 | D | 0.618 | neutral | None | None | None | None | I |
| R/N | 0.8939 | likely_pathogenic | 0.8773 | pathogenic | -0.059 | Destabilizing | 0.687 | D | 0.594 | neutral | None | None | None | None | I |
| R/P | 0.9005 | likely_pathogenic | 0.9012 | pathogenic | 0.197 | Stabilizing | 0.817 | D | 0.863 | deleterious | None | None | None | None | I |
| R/Q | 0.2135 | likely_benign | 0.1839 | benign | -0.174 | Destabilizing | 0.524 | D | 0.645 | neutral | None | None | None | None | I |
| R/S | 0.8114 | likely_pathogenic | 0.7777 | pathogenic | -0.479 | Destabilizing | 0.191 | N | 0.667 | prob.neutral | N | 0.458819213 | None | None | I |
| R/T | 0.4921 | ambiguous | 0.4213 | ambiguous | -0.265 | Destabilizing | 0.321 | N | 0.61 | neutral | N | 0.482240282 | None | None | I |
| R/V | 0.4669 | ambiguous | 0.4317 | ambiguous | 0.197 | Stabilizing | 0.687 | D | 0.78 | deleterious | None | None | None | None | I |
| R/W | 0.5012 | ambiguous | 0.4849 | ambiguous | -0.31 | Destabilizing | 0.981 | D | 0.895 | deleterious | None | None | None | None | I |
| R/Y | 0.7255 | likely_pathogenic | 0.7067 | pathogenic | 0.071 | Stabilizing | 0.931 | D | 0.855 | 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.