Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23338 | 70237;70238;70239 | chr2:178576120;178576119;178576118 | chr2:179440847;179440846;179440845 |
| N2AB | 21697 | 65314;65315;65316 | chr2:178576120;178576119;178576118 | chr2:179440847;179440846;179440845 |
| N2A | 20770 | 62533;62534;62535 | chr2:178576120;178576119;178576118 | chr2:179440847;179440846;179440845 |
| N2B | 14273 | 43042;43043;43044 | chr2:178576120;178576119;178576118 | chr2:179440847;179440846;179440845 |
| Novex-1 | 14398 | 43417;43418;43419 | chr2:178576120;178576119;178576118 | chr2:179440847;179440846;179440845 |
| Novex-2 | 14465 | 43618;43619;43620 | chr2:178576120;178576119;178576118 | chr2:179440847;179440846;179440845 |
| 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 | rs78916558  |
0.147 | 0.028 | D | 0.224 | 0.107 | None | gnomAD-2.1.1 | 3.57E-05 | None | None | None | None | N | None | 1.24008E-04 | 8.49E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 2.35E-05 | 0 |
| R/Q | rs78916558 |
0.147 | 0.028 | D | 0.224 | 0.107 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 1.93648E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs78916558 |
0.147 | 0.028 | D | 0.224 | 0.107 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/Q | rs78916558 |
0.147 | 0.028 | D | 0.224 | 0.107 | None | gnomAD-4.0.0 | 8.67728E-06 | None | None | None | None | N | None | 1.33344E-05 | 5.00033E-05 | None | 0 | 2.23404E-05 | None | 0 | 0 | 5.93427E-06 | 1.09835E-05 | 1.60087E-05 |
| R/W | rs773695377 |
-0.352 | 0.984 | N | 0.789 | 0.332 | 0.551220473365 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.15E-05 | None | 6.54E-05 | None | 0 | 7.82E-06 | 0 |
| R/W | rs773695377 |
-0.352 | 0.984 | N | 0.789 | 0.332 | 0.551220473365 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs773695377 |
-0.352 | 0.984 | N | 0.789 | 0.332 | 0.551220473365 | gnomAD-4.0.0 | 9.29804E-06 | None | None | None | None | N | None | 1.33586E-05 | 0 | None | 0 | 2.23374E-05 | None | 0 | 0 | 9.32523E-06 | 2.1966E-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 | 0.4939 | ambiguous | 0.5077 | ambiguous | -0.06 | Destabilizing | 0.08 | N | 0.465 | neutral | None | None | None | None | N |
| R/C | 0.3431 | ambiguous | 0.3691 | ambiguous | -0.189 | Destabilizing | 0.934 | D | 0.779 | deleterious | None | None | None | None | N |
| R/D | 0.7521 | likely_pathogenic | 0.7415 | pathogenic | -0.159 | Destabilizing | 0.147 | N | 0.603 | neutral | None | None | None | None | N |
| R/E | 0.3891 | ambiguous | 0.3767 | ambiguous | -0.112 | Destabilizing | 0.034 | N | 0.459 | neutral | None | None | None | None | N |
| R/F | 0.7278 | likely_pathogenic | 0.7478 | pathogenic | -0.326 | Destabilizing | 0.789 | D | 0.701 | prob.delet. | None | None | None | None | N |
| R/G | 0.4079 | ambiguous | 0.4088 | ambiguous | -0.23 | Destabilizing | 0.249 | N | 0.619 | neutral | N | 0.503589093 | None | None | N |
| R/H | 0.1696 | likely_benign | 0.1775 | benign | -0.675 | Destabilizing | 0.552 | D | 0.46 | neutral | None | None | None | None | N |
| R/I | 0.3662 | ambiguous | 0.3681 | ambiguous | 0.349 | Stabilizing | 0.552 | D | 0.725 | deleterious | None | None | None | None | N |
| R/K | 0.0946 | likely_benign | 0.0947 | benign | -0.144 | Destabilizing | 0.001 | N | 0.247 | neutral | None | None | None | None | N |
| R/L | 0.3627 | ambiguous | 0.372 | ambiguous | 0.349 | Stabilizing | 0.249 | N | 0.619 | neutral | D | 0.527762794 | None | None | N |
| R/M | 0.3317 | likely_benign | 0.3311 | benign | 0.005 | Stabilizing | 0.789 | D | 0.514 | neutral | None | None | None | None | N |
| R/N | 0.6466 | likely_pathogenic | 0.6426 | pathogenic | 0.097 | Stabilizing | 0.147 | N | 0.541 | neutral | None | None | None | None | N |
| R/P | 0.5908 | likely_pathogenic | 0.5962 | pathogenic | 0.232 | Stabilizing | 0.702 | D | 0.744 | deleterious | N | 0.503675213 | None | None | N |
| R/Q | 0.1343 | likely_benign | 0.1363 | benign | -0.025 | Destabilizing | 0.028 | N | 0.224 | neutral | D | 0.52602921 | None | None | N |
| R/S | 0.6491 | likely_pathogenic | 0.6481 | pathogenic | -0.234 | Destabilizing | 0.08 | N | 0.479 | neutral | None | None | None | None | N |
| R/T | 0.342 | ambiguous | 0.3398 | benign | -0.067 | Destabilizing | 0.147 | N | 0.589 | neutral | None | None | None | None | N |
| R/V | 0.4389 | ambiguous | 0.4466 | ambiguous | 0.232 | Stabilizing | 0.378 | N | 0.603 | neutral | None | None | None | None | N |
| R/W | 0.3082 | likely_benign | 0.3238 | benign | -0.397 | Destabilizing | 0.984 | D | 0.789 | deleterious | N | 0.493335651 | None | None | N |
| R/Y | 0.5791 | likely_pathogenic | 0.5868 | pathogenic | 0.004 | Stabilizing | 0.789 | D | 0.752 | deleterious | 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.