Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17020 | 51283;51284;51285 | chr2:178611071;178611070;178611069 | chr2:179475798;179475797;179475796 |
| N2AB | 15379 | 46360;46361;46362 | chr2:178611071;178611070;178611069 | chr2:179475798;179475797;179475796 |
| N2A | 14452 | 43579;43580;43581 | chr2:178611071;178611070;178611069 | chr2:179475798;179475797;179475796 |
| N2B | 7955 | 24088;24089;24090 | chr2:178611071;178611070;178611069 | chr2:179475798;179475797;179475796 |
| Novex-1 | 8080 | 24463;24464;24465 | chr2:178611071;178611070;178611069 | chr2:179475798;179475797;179475796 |
| Novex-2 | 8147 | 24664;24665;24666 | chr2:178611071;178611070;178611069 | chr2:179475798;179475797;179475796 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | rs1232414991  |
-0.263 | 0.338 | N | 0.412 | 0.112 | 0.104622674875 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| A/S | rs1232414991 |
-0.263 | 0.338 | N | 0.412 | 0.112 | 0.104622674875 | gnomAD-4.0.0 | 1.5933E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86241E-06 | 0 | 0 |
| A/T | None | None | 0.031 | N | 0.226 | 0.165 | 0.115124310173 | gnomAD-4.0.0 | 1.5933E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86241E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5038 | ambiguous | 0.4886 | ambiguous | -0.78 | Destabilizing | 0.991 | D | 0.442 | neutral | None | None | None | None | N |
| A/D | 0.144 | likely_benign | 0.1544 | benign | -0.642 | Destabilizing | 0.404 | N | 0.443 | neutral | None | None | None | None | N |
| A/E | 0.1384 | likely_benign | 0.1441 | benign | -0.794 | Destabilizing | 0.007 | N | 0.217 | neutral | N | 0.421162974 | None | None | N |
| A/F | 0.3825 | ambiguous | 0.4238 | ambiguous | -0.911 | Destabilizing | 0.967 | D | 0.565 | neutral | None | None | None | None | N |
| A/G | 0.1155 | likely_benign | 0.1158 | benign | -0.345 | Destabilizing | 0.003 | N | 0.206 | neutral | N | 0.45019593 | None | None | N |
| A/H | 0.4157 | ambiguous | 0.4304 | ambiguous | -0.32 | Destabilizing | 0.973 | D | 0.553 | neutral | None | None | None | None | N |
| A/I | 0.2415 | likely_benign | 0.2689 | benign | -0.381 | Destabilizing | 0.826 | D | 0.463 | neutral | None | None | None | None | N |
| A/K | 0.3516 | ambiguous | 0.376 | ambiguous | -0.732 | Destabilizing | 0.404 | N | 0.404 | neutral | None | None | None | None | N |
| A/L | 0.1701 | likely_benign | 0.1779 | benign | -0.381 | Destabilizing | 0.575 | D | 0.412 | neutral | None | None | None | None | N |
| A/M | 0.2262 | likely_benign | 0.2326 | benign | -0.46 | Destabilizing | 0.991 | D | 0.473 | neutral | None | None | None | None | N |
| A/N | 0.1676 | likely_benign | 0.1668 | benign | -0.4 | Destabilizing | 0.826 | D | 0.537 | neutral | None | None | None | None | N |
| A/P | 0.1491 | likely_benign | 0.1537 | benign | -0.323 | Destabilizing | 0.007 | N | 0.217 | neutral | N | 0.471263751 | None | None | N |
| A/Q | 0.2705 | likely_benign | 0.2787 | benign | -0.684 | Destabilizing | 0.704 | D | 0.464 | neutral | None | None | None | None | N |
| A/R | 0.3782 | ambiguous | 0.406 | ambiguous | -0.217 | Destabilizing | 0.826 | D | 0.463 | neutral | None | None | None | None | N |
| A/S | 0.0866 | likely_benign | 0.0837 | benign | -0.577 | Destabilizing | 0.338 | N | 0.412 | neutral | N | 0.436863179 | None | None | N |
| A/T | 0.086 | likely_benign | 0.0885 | benign | -0.654 | Destabilizing | 0.031 | N | 0.226 | neutral | N | 0.450896776 | None | None | N |
| A/V | 0.1328 | likely_benign | 0.1382 | benign | -0.323 | Destabilizing | 0.505 | D | 0.392 | neutral | N | 0.51261193 | None | None | N |
| A/W | 0.6958 | likely_pathogenic | 0.7302 | pathogenic | -1.045 | Destabilizing | 0.991 | D | 0.679 | prob.neutral | None | None | None | None | N |
| A/Y | 0.467 | ambiguous | 0.5052 | ambiguous | -0.715 | Destabilizing | 0.967 | D | 0.565 | 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.