Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22692 | 68299;68300;68301 | chr2:178578956;178578955;178578954 | chr2:179443683;179443682;179443681 |
| N2AB | 21051 | 63376;63377;63378 | chr2:178578956;178578955;178578954 | chr2:179443683;179443682;179443681 |
| N2A | 20124 | 60595;60596;60597 | chr2:178578956;178578955;178578954 | chr2:179443683;179443682;179443681 |
| N2B | 13627 | 41104;41105;41106 | chr2:178578956;178578955;178578954 | chr2:179443683;179443682;179443681 |
| Novex-1 | 13752 | 41479;41480;41481 | chr2:178578956;178578955;178578954 | chr2:179443683;179443682;179443681 |
| Novex-2 | 13819 | 41680;41681;41682 | chr2:178578956;178578955;178578954 | chr2:179443683;179443682;179443681 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs545399178  |
-0.306 | 0.08 | N | 0.333 | 0.075 | 0.440915056915 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 6.46E-05 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 1.65782E-04 |
| V/L | rs545399178 |
-0.306 | 0.08 | N | 0.333 | 0.075 | 0.440915056915 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/L | rs545399178 |
-0.306 | 0.08 | N | 0.333 | 0.075 | 0.440915056915 | gnomAD-4.0.0 | 4.95922E-06 | None | None | None | None | N | None | 2.67158E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08688E-06 | 0 | 0 |
| V/M | rs545399178 |
-0.245 | 0.81 | N | 0.417 | 0.224 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/M | rs545399178 |
-0.245 | 0.81 | N | 0.417 | 0.224 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs545399178 |
-0.245 | 0.81 | N | 0.417 | 0.224 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/M | rs545399178 |
-0.245 | 0.81 | N | 0.417 | 0.224 | None | gnomAD-4.0.0 | 1.85957E-06 | None | None | None | None | N | None | 4.00085E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3035 | likely_benign | 0.257 | benign | -0.931 | Destabilizing | 0.007 | N | 0.086 | neutral | N | 0.455315545 | None | None | N |
| V/C | 0.7847 | likely_pathogenic | 0.7601 | pathogenic | -0.738 | Destabilizing | 0.992 | D | 0.363 | neutral | None | None | None | None | N |
| V/D | 0.6028 | likely_pathogenic | 0.5696 | pathogenic | -0.726 | Destabilizing | 0.85 | D | 0.395 | neutral | None | None | None | None | N |
| V/E | 0.4307 | ambiguous | 0.4066 | ambiguous | -0.801 | Destabilizing | 0.549 | D | 0.33 | neutral | N | 0.472882585 | None | None | N |
| V/F | 0.2584 | likely_benign | 0.2301 | benign | -0.873 | Destabilizing | 0.85 | D | 0.399 | neutral | None | None | None | None | N |
| V/G | 0.3327 | likely_benign | 0.3069 | benign | -1.139 | Destabilizing | 0.379 | N | 0.335 | neutral | N | 0.520001741 | None | None | N |
| V/H | 0.6769 | likely_pathogenic | 0.6402 | pathogenic | -0.587 | Destabilizing | 0.992 | D | 0.401 | neutral | None | None | None | None | N |
| V/I | 0.0851 | likely_benign | 0.0795 | benign | -0.504 | Destabilizing | 0.005 | N | 0.157 | neutral | None | None | None | None | N |
| V/K | 0.5662 | likely_pathogenic | 0.5286 | ambiguous | -0.839 | Destabilizing | 0.617 | D | 0.331 | neutral | None | None | None | None | N |
| V/L | 0.2632 | likely_benign | 0.2336 | benign | -0.504 | Destabilizing | 0.08 | N | 0.333 | neutral | N | 0.474613381 | None | None | N |
| V/M | 0.1615 | likely_benign | 0.1476 | benign | -0.447 | Destabilizing | 0.81 | D | 0.417 | neutral | N | 0.489025473 | None | None | N |
| V/N | 0.3342 | likely_benign | 0.3112 | benign | -0.586 | Destabilizing | 0.85 | D | 0.415 | neutral | None | None | None | None | N |
| V/P | 0.9721 | likely_pathogenic | 0.9683 | pathogenic | -0.61 | Destabilizing | 0.92 | D | 0.396 | neutral | None | None | None | None | N |
| V/Q | 0.3899 | ambiguous | 0.3679 | ambiguous | -0.829 | Destabilizing | 0.85 | D | 0.414 | neutral | None | None | None | None | N |
| V/R | 0.5649 | likely_pathogenic | 0.5266 | ambiguous | -0.23 | Destabilizing | 0.85 | D | 0.425 | neutral | None | None | None | None | N |
| V/S | 0.3187 | likely_benign | 0.283 | benign | -0.999 | Destabilizing | 0.021 | N | 0.268 | neutral | None | None | None | None | N |
| V/T | 0.2779 | likely_benign | 0.248 | benign | -0.973 | Destabilizing | 0.447 | N | 0.292 | neutral | None | None | None | None | N |
| V/W | 0.8951 | likely_pathogenic | 0.8857 | pathogenic | -0.966 | Destabilizing | 0.992 | D | 0.524 | neutral | None | None | None | None | N |
| V/Y | 0.6321 | likely_pathogenic | 0.6073 | pathogenic | -0.695 | Destabilizing | 0.92 | D | 0.401 | 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.