Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21667 | 65224;65225;65226 | chr2:178584552;178584551;178584550 | chr2:179449279;179449278;179449277 |
| N2AB | 20026 | 60301;60302;60303 | chr2:178584552;178584551;178584550 | chr2:179449279;179449278;179449277 |
| N2A | 19099 | 57520;57521;57522 | chr2:178584552;178584551;178584550 | chr2:179449279;179449278;179449277 |
| N2B | 12602 | 38029;38030;38031 | chr2:178584552;178584551;178584550 | chr2:179449279;179449278;179449277 |
| Novex-1 | 12727 | 38404;38405;38406 | chr2:178584552;178584551;178584550 | chr2:179449279;179449278;179449277 |
| Novex-2 | 12794 | 38605;38606;38607 | chr2:178584552;178584551;178584550 | chr2:179449279;179449278;179449277 |
| 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 | rs758072872  |
0.091 | 0.082 | N | 0.189 | 0.13 | 0.115124310173 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 6.56E-05 | 0 | 0 | 1.94175E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs758072872 |
0.091 | 0.082 | N | 0.189 | 0.13 | 0.115124310173 | gnomAD-4.0.0 | 8.68252E-06 | None | None | None | None | N | None | 1.33372E-05 | 1.66795E-05 | None | 3.38158E-05 | 2.23944E-05 | None | 0 | 3.30797E-04 | 4.24114E-06 | 3.29765E-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 | 0.4253 | ambiguous | 0.342 | ambiguous | -0.675 | Destabilizing | 0.209 | N | 0.409 | neutral | None | None | None | None | N |
| R/C | 0.1582 | likely_benign | 0.1313 | benign | -0.569 | Destabilizing | 0.009 | N | 0.36 | neutral | None | None | None | None | N |
| R/D | 0.7372 | likely_pathogenic | 0.6578 | pathogenic | -0.117 | Destabilizing | 0.561 | D | 0.5 | neutral | None | None | None | None | N |
| R/E | 0.3894 | ambiguous | 0.3312 | benign | -0.001 | Destabilizing | 0.209 | N | 0.455 | neutral | None | None | None | None | N |
| R/F | 0.4502 | ambiguous | 0.3793 | ambiguous | -0.567 | Destabilizing | 0.818 | D | 0.458 | neutral | None | None | None | None | N |
| R/G | 0.4006 | ambiguous | 0.3079 | benign | -0.984 | Destabilizing | 0.832 | D | 0.472 | neutral | D | 0.52232997 | None | None | N |
| R/H | 0.0879 | likely_benign | 0.0811 | benign | -1.342 | Destabilizing | 0.004 | N | 0.305 | neutral | None | None | None | None | N |
| R/I | 0.2482 | likely_benign | 0.2043 | benign | 0.151 | Stabilizing | 0.39 | N | 0.497 | neutral | None | None | None | None | N |
| R/K | 0.1074 | likely_benign | 0.1004 | benign | -0.755 | Destabilizing | 0.209 | N | 0.448 | neutral | None | None | None | None | N |
| R/L | 0.2689 | likely_benign | 0.2152 | benign | 0.151 | Stabilizing | 0.336 | N | 0.418 | neutral | N | 0.493143214 | None | None | N |
| R/M | 0.3107 | likely_benign | 0.2475 | benign | -0.127 | Destabilizing | 0.901 | D | 0.504 | neutral | None | None | None | None | N |
| R/N | 0.5773 | likely_pathogenic | 0.502 | ambiguous | -0.204 | Destabilizing | 0.561 | D | 0.438 | neutral | None | None | None | None | N |
| R/P | 0.9466 | likely_pathogenic | 0.9178 | pathogenic | -0.103 | Destabilizing | 0.982 | D | 0.528 | neutral | N | 0.470776581 | None | None | N |
| R/Q | 0.1052 | likely_benign | 0.095 | benign | -0.374 | Destabilizing | 0.082 | N | 0.189 | neutral | N | 0.443829115 | None | None | N |
| R/S | 0.4868 | ambiguous | 0.4011 | ambiguous | -0.906 | Destabilizing | 0.345 | N | 0.46 | neutral | None | None | None | None | N |
| R/T | 0.2391 | likely_benign | 0.1898 | benign | -0.614 | Destabilizing | 0.561 | D | 0.479 | neutral | None | None | None | None | N |
| R/V | 0.2736 | likely_benign | 0.236 | benign | -0.103 | Destabilizing | 0.004 | N | 0.39 | neutral | None | None | None | None | N |
| R/W | 0.1877 | likely_benign | 0.1551 | benign | -0.266 | Destabilizing | 0.991 | D | 0.436 | neutral | None | None | None | None | N |
| R/Y | 0.3543 | ambiguous | 0.309 | benign | 0.046 | Stabilizing | 0.818 | D | 0.524 | 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.