Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17968 | 54127;54128;54129 | chr2:178605275;178605274;178605273 | chr2:179470002;179470001;179470000 |
| N2AB | 16327 | 49204;49205;49206 | chr2:178605275;178605274;178605273 | chr2:179470002;179470001;179470000 |
| N2A | 15400 | 46423;46424;46425 | chr2:178605275;178605274;178605273 | chr2:179470002;179470001;179470000 |
| N2B | 8903 | 26932;26933;26934 | chr2:178605275;178605274;178605273 | chr2:179470002;179470001;179470000 |
| Novex-1 | 9028 | 27307;27308;27309 | chr2:178605275;178605274;178605273 | chr2:179470002;179470001;179470000 |
| Novex-2 | 9095 | 27508;27509;27510 | chr2:178605275;178605274;178605273 | chr2:179470002;179470001;179470000 |
| 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 | rs776785175  |
-0.356 | 0.999 | N | 0.215 | 0.354 | 0.670247443365 | gnomAD-2.1.1 | 2.22E-05 | None | None | None | None | I | None | 0 | 6.52E-05 | None | 0 | 0 | None | 3.86E-05 | None | 0 | 1.93E-05 | 0 |
| R/C | rs776785175 |
-0.356 | 0.999 | N | 0.215 | 0.354 | 0.670247443365 | gnomAD-4.0.0 | 9.05292E-06 | None | None | None | None | I | None | 3.08471E-05 | 4.84379E-05 | None | 0 | 0 | None | 0 | 0 | 8.1839E-06 | 1.21862E-05 | 0 |
| R/H | rs200100660 |
-0.713 | 0.998 | N | 0.207 | 0.29 | None | gnomAD-2.1.1 | 8.76E-05 | None | None | None | None | I | None | 2.73112E-04 | 0 | None | 0 | 0 | None | 0 | None | 5E-05 | 1.43442E-04 | 0 |
| R/H | rs200100660 |
-0.713 | 0.998 | N | 0.207 | 0.29 | None | gnomAD-3.1.2 | 9.22E-05 | None | None | None | None | I | None | 1.9348E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.83E-05 | 0 | 0 |
| R/H | rs200100660 |
-0.713 | 0.998 | N | 0.207 | 0.29 | None | gnomAD-4.0.0 | 1.1059E-04 | None | None | None | None | I | None | 1.75771E-04 | 0 | None | 0 | 9.03669E-05 | None | 3.20205E-05 | 5.01672E-04 | 1.29995E-04 | 0 | 3.25415E-05 |
| R/S | rs776785175 |
None | 0.911 | N | 0.315 | 0.223 | 0.396794106654 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 0 | 0 | 0 |
| R/S | rs776785175 |
None | 0.911 | N | 0.315 | 0.223 | 0.396794106654 | gnomAD-4.0.0 | 6.58033E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.40136E-03 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5606 | ambiguous | 0.4022 | ambiguous | 0.172 | Stabilizing | 0.688 | D | 0.308 | neutral | None | None | None | None | I |
| R/C | 0.289 | likely_benign | 0.213 | benign | 0.024 | Stabilizing | 0.999 | D | 0.215 | neutral | N | 0.46481018 | None | None | I |
| R/D | 0.7804 | likely_pathogenic | 0.6406 | pathogenic | -0.123 | Destabilizing | 0.949 | D | 0.299 | neutral | None | None | None | None | I |
| R/E | 0.5663 | likely_pathogenic | 0.4215 | ambiguous | -0.062 | Destabilizing | 0.728 | D | 0.207 | neutral | None | None | None | None | I |
| R/F | 0.6772 | likely_pathogenic | 0.5862 | pathogenic | -0.057 | Destabilizing | 0.949 | D | 0.263 | neutral | None | None | None | None | I |
| R/G | 0.4566 | ambiguous | 0.2921 | benign | -0.01 | Destabilizing | 0.911 | D | 0.337 | neutral | N | 0.464116747 | None | None | I |
| R/H | 0.1479 | likely_benign | 0.1098 | benign | -0.597 | Destabilizing | 0.998 | D | 0.207 | neutral | N | 0.464290105 | None | None | I |
| R/I | 0.3984 | ambiguous | 0.315 | benign | 0.613 | Stabilizing | 0.728 | D | 0.347 | neutral | None | None | None | None | I |
| R/K | 0.1496 | likely_benign | 0.1207 | benign | 0.094 | Stabilizing | 0.007 | N | 0.087 | neutral | None | None | None | None | I |
| R/L | 0.3127 | likely_benign | 0.2393 | benign | 0.613 | Stabilizing | 0.013 | N | 0.149 | neutral | N | 0.390600423 | None | None | I |
| R/M | 0.4453 | ambiguous | 0.3407 | ambiguous | 0.105 | Stabilizing | 0.949 | D | 0.226 | neutral | None | None | None | None | I |
| R/N | 0.633 | likely_pathogenic | 0.482 | ambiguous | 0.274 | Stabilizing | 0.842 | D | 0.21 | neutral | None | None | None | None | I |
| R/P | 0.787 | likely_pathogenic | 0.6442 | pathogenic | 0.486 | Stabilizing | 0.986 | D | 0.285 | neutral | N | 0.464463464 | None | None | I |
| R/Q | 0.1548 | likely_benign | 0.1137 | benign | 0.221 | Stabilizing | 0.842 | D | 0.213 | neutral | None | None | None | None | I |
| R/S | 0.6175 | likely_pathogenic | 0.4386 | ambiguous | 0.052 | Stabilizing | 0.911 | D | 0.315 | neutral | N | 0.462383164 | None | None | I |
| R/T | 0.407 | ambiguous | 0.2687 | benign | 0.237 | Stabilizing | 0.842 | D | 0.321 | neutral | None | None | None | None | I |
| R/V | 0.46 | ambiguous | 0.3646 | ambiguous | 0.486 | Stabilizing | 0.728 | D | 0.317 | neutral | None | None | None | None | I |
| R/W | 0.3533 | ambiguous | 0.2815 | benign | -0.197 | Destabilizing | 0.998 | D | 0.235 | neutral | None | None | None | None | I |
| R/Y | 0.5349 | ambiguous | 0.429 | ambiguous | 0.222 | Stabilizing | 0.991 | D | 0.269 | 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.