Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14409 | 43450;43451;43452 | chr2:178632781;178632780;178632779 | chr2:179497508;179497507;179497506 |
| N2AB | 12768 | 38527;38528;38529 | chr2:178632781;178632780;178632779 | chr2:179497508;179497507;179497506 |
| N2A | 11841 | 35746;35747;35748 | chr2:178632781;178632780;178632779 | chr2:179497508;179497507;179497506 |
| N2B | 5344 | 16255;16256;16257 | chr2:178632781;178632780;178632779 | chr2:179497508;179497507;179497506 |
| Novex-1 | 5469 | 16630;16631;16632 | chr2:178632781;178632780;178632779 | chr2:179497508;179497507;179497506 |
| Novex-2 | 5536 | 16831;16832;16833 | chr2:178632781;178632780;178632779 | chr2:179497508;179497507;179497506 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs1427373218  |
-0.432 | 0.996 | D | 0.406 | 0.435 | 0.752625438931 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.82E-05 | None | 0 | 0 | 0 |
| I/M | rs1427373218 |
-0.432 | 0.996 | D | 0.406 | 0.435 | 0.752625438931 | gnomAD-4.0.0 | 2.7383E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.63962E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6399 | likely_pathogenic | 0.5334 | ambiguous | -1.014 | Destabilizing | 0.579 | D | 0.365 | neutral | None | None | None | None | N |
| I/C | 0.8528 | likely_pathogenic | 0.8075 | pathogenic | -0.863 | Destabilizing | 0.999 | D | 0.393 | neutral | None | None | None | None | N |
| I/D | 0.8187 | likely_pathogenic | 0.7611 | pathogenic | -0.05 | Destabilizing | 0.939 | D | 0.401 | neutral | None | None | None | None | N |
| I/E | 0.7403 | likely_pathogenic | 0.6777 | pathogenic | -0.02 | Destabilizing | 0.939 | D | 0.387 | neutral | None | None | None | None | N |
| I/F | 0.2936 | likely_benign | 0.2228 | benign | -0.492 | Destabilizing | 0.996 | D | 0.387 | neutral | D | 0.544993568 | None | None | N |
| I/G | 0.8375 | likely_pathogenic | 0.7626 | pathogenic | -1.297 | Destabilizing | 0.939 | D | 0.399 | neutral | None | None | None | None | N |
| I/H | 0.6204 | likely_pathogenic | 0.5531 | ambiguous | -0.224 | Destabilizing | 0.999 | D | 0.413 | neutral | None | None | None | None | N |
| I/K | 0.5605 | ambiguous | 0.5133 | ambiguous | -0.544 | Destabilizing | 0.939 | D | 0.407 | neutral | None | None | None | None | N |
| I/L | 0.1419 | likely_benign | 0.1186 | benign | -0.321 | Destabilizing | 0.675 | D | 0.258 | neutral | N | 0.476681365 | None | None | N |
| I/M | 0.178 | likely_benign | 0.147 | benign | -0.564 | Destabilizing | 0.996 | D | 0.406 | neutral | D | 0.545095579 | None | None | N |
| I/N | 0.4045 | ambiguous | 0.3237 | benign | -0.622 | Destabilizing | 0.92 | D | 0.399 | neutral | N | 0.46780481 | None | None | N |
| I/P | 0.9048 | likely_pathogenic | 0.9068 | pathogenic | -0.521 | Destabilizing | 0.991 | D | 0.415 | neutral | None | None | None | None | N |
| I/Q | 0.5852 | likely_pathogenic | 0.5194 | ambiguous | -0.658 | Destabilizing | 0.991 | D | 0.437 | neutral | None | None | None | None | N |
| I/R | 0.4314 | ambiguous | 0.3736 | ambiguous | -0.099 | Destabilizing | 0.991 | D | 0.425 | neutral | None | None | None | None | N |
| I/S | 0.4706 | ambiguous | 0.3716 | ambiguous | -1.247 | Destabilizing | 0.159 | N | 0.212 | neutral | N | 0.413668139 | None | None | N |
| I/T | 0.4498 | ambiguous | 0.3517 | ambiguous | -1.088 | Destabilizing | 0.061 | N | 0.211 | neutral | N | 0.464264276 | None | None | N |
| I/V | 0.1585 | likely_benign | 0.1304 | benign | -0.521 | Destabilizing | 0.675 | D | 0.269 | neutral | N | 0.521464138 | None | None | N |
| I/W | 0.8758 | likely_pathogenic | 0.8532 | pathogenic | -0.535 | Destabilizing | 0.999 | D | 0.455 | neutral | None | None | None | None | N |
| I/Y | 0.5898 | likely_pathogenic | 0.541 | ambiguous | -0.304 | Destabilizing | 0.997 | D | 0.407 | 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.