Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7796 | 23611;23612;23613 | chr2:178720256;178720255;178720254 | chr2:179584983;179584982;179584981 |
| N2AB | 7479 | 22660;22661;22662 | chr2:178720256;178720255;178720254 | chr2:179584983;179584982;179584981 |
| N2A | 6552 | 19879;19880;19881 | chr2:178720256;178720255;178720254 | chr2:179584983;179584982;179584981 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 | rs267599059  |
0.095 | 0.956 | N | 0.267 | 0.233 | None | gnomAD-2.1.1 | 7.59E-05 | None | None | None | None | N | None | 7.45342E-04 | 5.72E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.91E-06 | 0 |
| R/Q | rs267599059 |
0.095 | 0.956 | N | 0.267 | 0.233 | None | gnomAD-3.1.2 | 2.03813E-04 | None | None | None | None | N | None | 6.51607E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 9.57854E-04 |
| R/Q | rs267599059 |
0.095 | 0.956 | N | 0.267 | 0.233 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs267599059 |
0.095 | 0.956 | N | 0.267 | 0.233 | None | gnomAD-4.0.0 | 3.856E-05 | None | None | None | None | N | None | 5.47923E-04 | 5.0388E-05 | None | 0 | 0 | None | 0 | 0 | 9.35303E-06 | 1.10818E-05 | 9.64351E-05 |
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 | 0.3439 | ambiguous | 0.3845 | ambiguous | -0.228 | Destabilizing | 0.237 | N | 0.202 | neutral | None | None | None | None | N |
| R/C | 0.2055 | likely_benign | 0.2222 | benign | -0.389 | Destabilizing | 0.996 | D | 0.238 | neutral | None | None | None | None | N |
| R/D | 0.7281 | likely_pathogenic | 0.7801 | pathogenic | -0.008 | Destabilizing | 0.775 | D | 0.313 | neutral | None | None | None | None | N |
| R/E | 0.4312 | ambiguous | 0.4801 | ambiguous | 0.109 | Stabilizing | 0.299 | N | 0.185 | neutral | None | None | None | None | N |
| R/F | 0.4944 | ambiguous | 0.5345 | ambiguous | -0.174 | Destabilizing | 0.907 | D | 0.279 | neutral | None | None | None | None | N |
| R/G | 0.2961 | likely_benign | 0.3426 | ambiguous | -0.503 | Destabilizing | 0.009 | N | 0.207 | neutral | D | 0.522029878 | None | None | N |
| R/H | 0.0999 | likely_benign | 0.1127 | benign | -0.927 | Destabilizing | 0.969 | D | 0.304 | neutral | None | None | None | None | N |
| R/I | 0.2266 | likely_benign | 0.2382 | benign | 0.487 | Stabilizing | 0.417 | N | 0.306 | neutral | None | None | None | None | N |
| R/K | 0.1211 | likely_benign | 0.1252 | benign | -0.286 | Destabilizing | 0.145 | N | 0.257 | neutral | None | None | None | None | N |
| R/L | 0.2272 | likely_benign | 0.2543 | benign | 0.487 | Stabilizing | 0.361 | N | 0.285 | neutral | N | 0.485821368 | None | None | N |
| R/M | 0.2916 | likely_benign | 0.3216 | benign | -0.08 | Destabilizing | 0.91 | D | 0.279 | neutral | None | None | None | None | N |
| R/N | 0.5272 | ambiguous | 0.5953 | pathogenic | -0.076 | Destabilizing | 0.775 | D | 0.183 | neutral | None | None | None | None | N |
| R/P | 0.9325 | likely_pathogenic | 0.9409 | pathogenic | 0.27 | Stabilizing | 0.931 | D | 0.333 | neutral | N | 0.510927063 | None | None | N |
| R/Q | 0.1115 | likely_benign | 0.1217 | benign | -0.117 | Destabilizing | 0.956 | D | 0.267 | neutral | N | 0.509142535 | None | None | N |
| R/S | 0.3881 | ambiguous | 0.4475 | ambiguous | -0.565 | Destabilizing | 0.053 | N | 0.19 | neutral | None | None | None | None | N |
| R/T | 0.2128 | likely_benign | 0.2402 | benign | -0.276 | Destabilizing | 0.019 | N | 0.187 | neutral | None | None | None | None | N |
| R/V | 0.2712 | likely_benign | 0.285 | benign | 0.27 | Stabilizing | 0.014 | N | 0.291 | neutral | None | None | None | None | N |
| R/W | 0.2109 | likely_benign | 0.2351 | benign | -0.069 | Destabilizing | 0.998 | D | 0.253 | neutral | None | None | None | None | N |
| R/Y | 0.3612 | ambiguous | 0.3982 | ambiguous | 0.287 | Stabilizing | 0.967 | D | 0.278 | 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.