Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28872 | 86839;86840;86841 | chr2:178559518;178559517;178559516 | chr2:179424245;179424244;179424243 |
| N2AB | 27231 | 81916;81917;81918 | chr2:178559518;178559517;178559516 | chr2:179424245;179424244;179424243 |
| N2A | 26304 | 79135;79136;79137 | chr2:178559518;178559517;178559516 | chr2:179424245;179424244;179424243 |
| N2B | 19807 | 59644;59645;59646 | chr2:178559518;178559517;178559516 | chr2:179424245;179424244;179424243 |
| Novex-1 | 19932 | 60019;60020;60021 | chr2:178559518;178559517;178559516 | chr2:179424245;179424244;179424243 |
| Novex-2 | 19999 | 60220;60221;60222 | chr2:178559518;178559517;178559516 | chr2:179424245;179424244;179424243 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.01 | N | 0.121 | 0.065 | 0.146414634003 | gnomAD-4.0.0 | 1.59137E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43291E-05 | 0 |
| D/H | rs1337280647  |
-0.848 | 1.0 | N | 0.681 | 0.384 | 0.368183359018 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs1337280647 |
-0.848 | 1.0 | N | 0.681 | 0.384 | 0.368183359018 | gnomAD-4.0.0 | 6.84239E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.51965E-05 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs1337280647 |
-0.322 | 0.988 | N | 0.607 | 0.369 | 0.263140351381 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| D/N | rs1337280647 |
-0.322 | 0.988 | N | 0.607 | 0.369 | 0.263140351381 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs1337280647 |
-0.322 | 0.988 | N | 0.607 | 0.369 | 0.263140351381 | gnomAD-4.0.0 | 1.85914E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54292E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.8375 | likely_pathogenic | 0.8411 | pathogenic | -0.15 | Destabilizing | 0.942 | D | 0.64 | neutral | N | 0.477916151 | None | None | I |
| D/C | 0.9672 | likely_pathogenic | 0.9686 | pathogenic | 0.169 | Stabilizing | 0.998 | D | 0.701 | prob.neutral | None | None | None | None | I |
| D/E | 0.6389 | likely_pathogenic | 0.6545 | pathogenic | -0.669 | Destabilizing | 0.01 | N | 0.121 | neutral | N | 0.500626547 | None | None | I |
| D/F | 0.9763 | likely_pathogenic | 0.9737 | pathogenic | -0.44 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| D/G | 0.8451 | likely_pathogenic | 0.8304 | pathogenic | -0.401 | Destabilizing | 0.96 | D | 0.616 | neutral | N | 0.502149699 | None | None | I |
| D/H | 0.9063 | likely_pathogenic | 0.8931 | pathogenic | -0.838 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.496616291 | None | None | I |
| D/I | 0.9375 | likely_pathogenic | 0.9394 | pathogenic | 0.471 | Stabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | I |
| D/K | 0.9626 | likely_pathogenic | 0.9569 | pathogenic | 0.013 | Stabilizing | 0.987 | D | 0.621 | neutral | None | None | None | None | I |
| D/L | 0.9426 | likely_pathogenic | 0.9395 | pathogenic | 0.471 | Stabilizing | 0.998 | D | 0.725 | prob.delet. | None | None | None | None | I |
| D/M | 0.9776 | likely_pathogenic | 0.978 | pathogenic | 0.884 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | I |
| D/N | 0.2986 | likely_benign | 0.2729 | benign | -0.189 | Destabilizing | 0.988 | D | 0.607 | neutral | N | 0.500685262 | None | None | I |
| D/P | 0.9821 | likely_pathogenic | 0.9814 | pathogenic | 0.289 | Stabilizing | 0.97 | D | 0.701 | prob.neutral | None | None | None | None | I |
| D/Q | 0.9352 | likely_pathogenic | 0.9293 | pathogenic | -0.13 | Destabilizing | 0.99 | D | 0.635 | neutral | None | None | None | None | I |
| D/R | 0.9572 | likely_pathogenic | 0.9506 | pathogenic | -0.088 | Destabilizing | 0.996 | D | 0.719 | prob.delet. | None | None | None | None | I |
| D/S | 0.5952 | likely_pathogenic | 0.5749 | pathogenic | -0.329 | Destabilizing | 0.955 | D | 0.546 | neutral | None | None | None | None | I |
| D/T | 0.8053 | likely_pathogenic | 0.7989 | pathogenic | -0.136 | Destabilizing | 0.985 | D | 0.615 | neutral | None | None | None | None | I |
| D/V | 0.8635 | likely_pathogenic | 0.8662 | pathogenic | 0.289 | Stabilizing | 0.986 | D | 0.72 | prob.delet. | N | 0.489525946 | None | None | I |
| D/W | 0.9949 | likely_pathogenic | 0.9944 | pathogenic | -0.492 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | I |
| D/Y | 0.8525 | likely_pathogenic | 0.841 | pathogenic | -0.254 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.520253954 | 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.