Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33127 | 99604;99605;99606 | chr2:178537828;178537827;178537826 | chr2:179402555;179402554;179402553 |
| N2AB | 31486 | 94681;94682;94683 | chr2:178537828;178537827;178537826 | chr2:179402555;179402554;179402553 |
| N2A | 30559 | 91900;91901;91902 | chr2:178537828;178537827;178537826 | chr2:179402555;179402554;179402553 |
| N2B | 24062 | 72409;72410;72411 | chr2:178537828;178537827;178537826 | chr2:179402555;179402554;179402553 |
| Novex-1 | 24187 | 72784;72785;72786 | chr2:178537828;178537827;178537826 | chr2:179402555;179402554;179402553 |
| Novex-2 | 24254 | 72985;72986;72987 | chr2:178537828;178537827;178537826 | chr2:179402555;179402554;179402553 |
| 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/K | rs1205888266  |
0.092 | 0.067 | N | 0.405 | 0.204 | 0.322230723748 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs1205888266 |
0.092 | 0.067 | N | 0.405 | 0.204 | 0.322230723748 | gnomAD-4.0.0 | 1.59159E-06 | None | None | None | None | I | None | 0 | 2.2876E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs747615650 |
-0.105 | 0.978 | N | 0.627 | 0.35 | 0.28798054836 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.88E-06 | 0 |
| R/S | rs747615650 |
-0.105 | 0.978 | N | 0.627 | 0.35 | 0.28798054836 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs747615650 |
-0.105 | 0.978 | N | 0.627 | 0.35 | 0.28798054836 | gnomAD-4.0.0 | 3.0988E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69529E-06 | 3.29504E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.922 | likely_pathogenic | 0.9226 | pathogenic | 0.032 | Stabilizing | 0.983 | D | 0.623 | neutral | None | None | None | None | I |
| R/C | 0.6158 | likely_pathogenic | 0.5837 | pathogenic | -0.32 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | I |
| R/D | 0.9607 | likely_pathogenic | 0.9652 | pathogenic | -0.377 | Destabilizing | 0.998 | D | 0.581 | neutral | None | None | None | None | I |
| R/E | 0.8316 | likely_pathogenic | 0.8422 | pathogenic | -0.341 | Destabilizing | 0.947 | D | 0.615 | neutral | None | None | None | None | I |
| R/F | 0.8605 | likely_pathogenic | 0.8688 | pathogenic | -0.316 | Destabilizing | 0.998 | D | 0.619 | neutral | None | None | None | None | I |
| R/G | 0.8825 | likely_pathogenic | 0.8769 | pathogenic | -0.09 | Destabilizing | 0.989 | D | 0.567 | neutral | N | 0.486228389 | None | None | I |
| R/H | 0.2842 | likely_benign | 0.272 | benign | -0.583 | Destabilizing | 0.998 | D | 0.617 | neutral | None | None | None | None | I |
| R/I | 0.6983 | likely_pathogenic | 0.6917 | pathogenic | 0.306 | Stabilizing | 0.998 | D | 0.617 | neutral | None | None | None | None | I |
| R/K | 0.2654 | likely_benign | 0.267 | benign | -0.23 | Destabilizing | 0.067 | N | 0.405 | neutral | N | 0.407631533 | None | None | I |
| R/L | 0.6692 | likely_pathogenic | 0.6662 | pathogenic | 0.306 | Stabilizing | 0.98 | D | 0.567 | neutral | None | None | None | None | I |
| R/M | 0.7754 | likely_pathogenic | 0.7625 | pathogenic | -0.145 | Destabilizing | 0.999 | D | 0.589 | neutral | N | 0.486575106 | None | None | I |
| R/N | 0.8991 | likely_pathogenic | 0.9127 | pathogenic | -0.196 | Destabilizing | 0.998 | D | 0.596 | neutral | None | None | None | None | I |
| R/P | 0.9845 | likely_pathogenic | 0.9872 | pathogenic | 0.231 | Stabilizing | 0.999 | D | 0.591 | neutral | None | None | None | None | I |
| R/Q | 0.3103 | likely_benign | 0.3006 | benign | -0.205 | Destabilizing | 0.994 | D | 0.594 | neutral | None | None | None | None | I |
| R/S | 0.8997 | likely_pathogenic | 0.9055 | pathogenic | -0.322 | Destabilizing | 0.978 | D | 0.627 | neutral | N | 0.392278078 | None | None | I |
| R/T | 0.8161 | likely_pathogenic | 0.8234 | pathogenic | -0.19 | Destabilizing | 0.997 | D | 0.583 | neutral | N | 0.427929447 | None | None | I |
| R/V | 0.7912 | likely_pathogenic | 0.7994 | pathogenic | 0.231 | Stabilizing | 0.992 | D | 0.598 | neutral | None | None | None | None | I |
| R/W | 0.5325 | ambiguous | 0.5179 | ambiguous | -0.536 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.486575106 | None | None | I |
| R/Y | 0.7228 | likely_pathogenic | 0.7236 | pathogenic | -0.135 | Destabilizing | 0.998 | D | 0.609 | 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.