Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16055 | 48388;48389;48390 | chr2:178616628;178616627;178616626 | chr2:179481355;179481354;179481353 |
| N2AB | 14414 | 43465;43466;43467 | chr2:178616628;178616627;178616626 | chr2:179481355;179481354;179481353 |
| N2A | 13487 | 40684;40685;40686 | chr2:178616628;178616627;178616626 | chr2:179481355;179481354;179481353 |
| N2B | 6990 | 21193;21194;21195 | chr2:178616628;178616627;178616626 | chr2:179481355;179481354;179481353 |
| Novex-1 | 7115 | 21568;21569;21570 | chr2:178616628;178616627;178616626 | chr2:179481355;179481354;179481353 |
| Novex-2 | 7182 | 21769;21770;21771 | chr2:178616628;178616627;178616626 | chr2:179481355;179481354;179481353 |
| 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/C | rs1012450335  |
-0.283 | None | N | 0.229 | 0.151 | None | gnomAD-2.1.1 | 7.2E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.21E-05 | None | 3.3E-05 | None | 0 | 0 | 0 |
| R/C | rs1012450335 |
-0.283 | None | N | 0.229 | 0.151 | None | gnomAD-3.1.2 | 6.6E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.95313E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs1012450335 |
-0.283 | None | N | 0.229 | 0.151 | None | gnomAD-4.0.0 | 7.44848E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.24125E-05 | None | 0 | 0 | 5.93874E-06 | 4.40713E-05 | 0 |
| R/H | rs72677238 |
-1.176 | 0.768 | N | 0.384 | 0.149 | None | gnomAD-2.1.1 | 1.21551E-04 | None | None | None | None | N | None | 0 | 2.92E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.41602E-04 | 3.35008E-04 |
| R/H | rs72677238 |
-1.176 | 0.768 | N | 0.384 | 0.149 | None | gnomAD-3.1.2 | 3.3E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.37E-05 | 0 | 0 |
| R/H | rs72677238 |
-1.176 | 0.768 | N | 0.384 | 0.149 | None | gnomAD-4.0.0 | 1.07402E-04 | None | None | None | None | N | None | 4.02339E-05 | 5.03373E-05 | None | 0 | 0 | None | 0 | 6.59848E-04 | 1.25573E-04 | 0 | 2.40778E-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 | 0.2588 | likely_benign | 0.2981 | benign | -0.41 | Destabilizing | None | N | 0.061 | neutral | None | None | None | None | N |
| R/C | 0.1234 | likely_benign | 0.1402 | benign | -0.304 | Destabilizing | None | N | 0.229 | neutral | N | 0.438514128 | None | None | N |
| R/D | 0.7171 | likely_pathogenic | 0.7816 | pathogenic | -0.075 | Destabilizing | 0.035 | N | 0.527 | neutral | None | None | None | None | N |
| R/E | 0.3912 | ambiguous | 0.4395 | ambiguous | 0.007 | Stabilizing | 0.015 | N | 0.223 | neutral | None | None | None | None | N |
| R/F | 0.4881 | ambiguous | 0.5751 | pathogenic | -0.485 | Destabilizing | 0.439 | N | 0.405 | neutral | None | None | None | None | N |
| R/G | 0.2606 | likely_benign | 0.3048 | benign | -0.665 | Destabilizing | None | N | 0.079 | neutral | D | 0.561409819 | None | None | N |
| R/H | 0.136 | likely_benign | 0.1595 | benign | -1.12 | Destabilizing | 0.768 | D | 0.384 | neutral | N | 0.496339939 | None | None | N |
| R/I | 0.2478 | likely_benign | 0.2909 | benign | 0.249 | Stabilizing | 0.068 | N | 0.447 | neutral | None | None | None | None | N |
| R/K | 0.1054 | likely_benign | 0.1175 | benign | -0.456 | Destabilizing | 0.015 | N | 0.223 | neutral | None | None | None | None | N |
| R/L | 0.2005 | likely_benign | 0.2282 | benign | 0.249 | Stabilizing | 0.028 | N | 0.311 | neutral | N | 0.440791762 | None | None | N |
| R/M | 0.2694 | likely_benign | 0.3149 | benign | -0.007 | Destabilizing | 0.439 | N | 0.386 | neutral | None | None | None | None | N |
| R/N | 0.5285 | ambiguous | 0.6202 | pathogenic | 0.07 | Stabilizing | 0.035 | N | 0.295 | neutral | None | None | None | None | N |
| R/P | 0.2423 | likely_benign | 0.2334 | benign | 0.05 | Stabilizing | None | N | 0.173 | neutral | N | 0.44074502 | None | None | N |
| R/Q | 0.1133 | likely_benign | 0.1247 | benign | -0.137 | Destabilizing | 0.068 | N | 0.347 | neutral | None | None | None | None | N |
| R/S | 0.3447 | ambiguous | 0.4168 | ambiguous | -0.515 | Destabilizing | 0.001 | N | 0.118 | neutral | N | 0.453648559 | None | None | N |
| R/T | 0.2101 | likely_benign | 0.2591 | benign | -0.277 | Destabilizing | 0.007 | N | 0.295 | neutral | None | None | None | None | N |
| R/V | 0.2846 | likely_benign | 0.3206 | benign | 0.05 | Stabilizing | 0.035 | N | 0.467 | neutral | None | None | None | None | N |
| R/W | 0.2342 | likely_benign | 0.2774 | benign | -0.313 | Destabilizing | 0.747 | D | 0.316 | neutral | None | None | None | None | N |
| R/Y | 0.3566 | ambiguous | 0.4326 | ambiguous | 0.037 | Stabilizing | 0.439 | N | 0.425 | 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.