Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26547 | 79864;79865;79866 | chr2:178566493;178566492;178566491 | chr2:179431220;179431219;179431218 |
| N2AB | 24906 | 74941;74942;74943 | chr2:178566493;178566492;178566491 | chr2:179431220;179431219;179431218 |
| N2A | 23979 | 72160;72161;72162 | chr2:178566493;178566492;178566491 | chr2:179431220;179431219;179431218 |
| N2B | 17482 | 52669;52670;52671 | chr2:178566493;178566492;178566491 | chr2:179431220;179431219;179431218 |
| Novex-1 | 17607 | 53044;53045;53046 | chr2:178566493;178566492;178566491 | chr2:179431220;179431219;179431218 |
| Novex-2 | 17674 | 53245;53246;53247 | chr2:178566493;178566492;178566491 | chr2:179431220;179431219;179431218 |
| 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/Q | rs771534555  |
-0.591 | 0.924 | N | 0.491 | 0.179 | 0.128392430309 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | I | None | 1.6533E-04 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.13E-05 | 0 |
| R/Q | rs771534555 |
-0.591 | 0.924 | N | 0.491 | 0.179 | 0.128392430309 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs771534555 |
-0.591 | 0.924 | N | 0.491 | 0.179 | 0.128392430309 | gnomAD-4.0.0 | 2.60335E-05 | None | None | None | None | I | None | 6.67771E-05 | 0 | None | 0 | 2.22955E-05 | None | 0 | 0 | 2.37353E-05 | 1.09791E-05 | 1.12111E-04 |
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 | 0.2822 | likely_benign | 0.2686 | benign | -0.242 | Destabilizing | 0.373 | N | 0.503 | neutral | None | None | None | None | I |
| R/C | 0.1325 | likely_benign | 0.1323 | benign | -0.478 | Destabilizing | 0.996 | D | 0.639 | neutral | None | None | None | None | I |
| R/D | 0.5019 | ambiguous | 0.4883 | ambiguous | -0.021 | Destabilizing | 0.742 | D | 0.567 | neutral | None | None | None | None | I |
| R/E | 0.266 | likely_benign | 0.25 | benign | 0.104 | Stabilizing | 0.373 | N | 0.513 | neutral | None | None | None | None | I |
| R/F | 0.4577 | ambiguous | 0.452 | ambiguous | -0.198 | Destabilizing | 0.984 | D | 0.625 | neutral | None | None | None | None | I |
| R/G | 0.206 | likely_benign | 0.2018 | benign | -0.51 | Destabilizing | 0.846 | D | 0.531 | neutral | N | 0.477269684 | None | None | I |
| R/H | 0.0853 | likely_benign | 0.0841 | benign | -0.91 | Destabilizing | 0.953 | D | 0.555 | neutral | None | None | None | None | I |
| R/I | 0.2293 | likely_benign | 0.2281 | benign | 0.456 | Stabilizing | 0.953 | D | 0.615 | neutral | None | None | None | None | I |
| R/K | 0.0814 | likely_benign | 0.0824 | benign | -0.225 | Destabilizing | 0.001 | N | 0.294 | neutral | None | None | None | None | I |
| R/L | 0.2302 | likely_benign | 0.2185 | benign | 0.456 | Stabilizing | 0.846 | D | 0.531 | neutral | N | 0.492700497 | None | None | I |
| R/M | 0.2338 | likely_benign | 0.2333 | benign | -0.172 | Destabilizing | 0.984 | D | 0.589 | neutral | None | None | None | None | I |
| R/N | 0.3332 | likely_benign | 0.3225 | benign | -0.147 | Destabilizing | 0.742 | D | 0.473 | neutral | None | None | None | None | I |
| R/P | 0.8614 | likely_pathogenic | 0.8472 | pathogenic | 0.244 | Stabilizing | 0.975 | D | 0.583 | neutral | N | 0.465321894 | None | None | I |
| R/Q | 0.0922 | likely_benign | 0.0893 | benign | -0.151 | Destabilizing | 0.924 | D | 0.491 | neutral | N | 0.428630376 | None | None | I |
| R/S | 0.2641 | likely_benign | 0.2602 | benign | -0.623 | Destabilizing | 0.742 | D | 0.5 | neutral | None | None | None | None | I |
| R/T | 0.1349 | likely_benign | 0.1293 | benign | -0.324 | Destabilizing | 0.742 | D | 0.491 | neutral | None | None | None | None | I |
| R/V | 0.2634 | likely_benign | 0.2581 | benign | 0.244 | Stabilizing | 0.91 | D | 0.579 | neutral | None | None | None | None | I |
| R/W | 0.2121 | likely_benign | 0.2103 | benign | -0.122 | Destabilizing | 0.996 | D | 0.662 | neutral | None | None | None | None | I |
| R/Y | 0.3035 | likely_benign | 0.3091 | benign | 0.24 | Stabilizing | 0.984 | D | 0.605 | neutral | 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.