Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17472 | 52639;52640;52641 | chr2:178608469;178608468;178608467 | chr2:179473196;179473195;179473194 |
| N2AB | 15831 | 47716;47717;47718 | chr2:178608469;178608468;178608467 | chr2:179473196;179473195;179473194 |
| N2A | 14904 | 44935;44936;44937 | chr2:178608469;178608468;178608467 | chr2:179473196;179473195;179473194 |
| N2B | 8407 | 25444;25445;25446 | chr2:178608469;178608468;178608467 | chr2:179473196;179473195;179473194 |
| Novex-1 | 8532 | 25819;25820;25821 | chr2:178608469;178608468;178608467 | chr2:179473196;179473195;179473194 |
| Novex-2 | 8599 | 26020;26021;26022 | chr2:178608469;178608468;178608467 | chr2:179473196;179473195;179473194 |
| 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 | rs367794487  |
-0.52 | 0.117 | N | 0.439 | 0.072 | 0.351614576976 | gnomAD-2.1.1 | 4.47E-06 | None | None | None | None | N | None | 7.04E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs367794487 |
-0.52 | 0.117 | N | 0.439 | 0.072 | 0.351614576976 | gnomAD-4.0.0 | 6.93613E-07 | None | None | None | None | N | None | 3.07541E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs727503614 |
-0.299 | 0.993 | N | 0.748 | 0.4 | 0.407082143382 | gnomAD-2.1.1 | 9.38E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.03E-05 | 0 |
| D/N | rs727503614 |
-0.299 | 0.993 | N | 0.748 | 0.4 | 0.407082143382 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs727503614 |
-0.299 | 0.993 | N | 0.748 | 0.4 | 0.407082143382 | gnomAD-4.0.0 | 2.53076E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.42784E-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 | 0.1618 | likely_benign | 0.1501 | benign | -0.405 | Destabilizing | 0.977 | D | 0.752 | deleterious | D | 0.523079332 | None | None | N |
| D/C | 0.6327 | likely_pathogenic | 0.6184 | pathogenic | -0.159 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| D/E | 0.1624 | likely_benign | 0.1462 | benign | -0.661 | Destabilizing | 0.117 | N | 0.439 | neutral | N | 0.483656939 | None | None | N |
| D/F | 0.7233 | likely_pathogenic | 0.7172 | pathogenic | -0.254 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| D/G | 0.1848 | likely_benign | 0.1669 | benign | -0.706 | Destabilizing | 0.989 | D | 0.746 | deleterious | N | 0.466071256 | None | None | N |
| D/H | 0.4257 | ambiguous | 0.4125 | ambiguous | -0.595 | Destabilizing | 0.999 | D | 0.811 | deleterious | N | 0.506744828 | None | None | N |
| D/I | 0.5423 | ambiguous | 0.5256 | ambiguous | 0.368 | Stabilizing | 0.998 | D | 0.805 | deleterious | None | None | None | None | N |
| D/K | 0.5114 | ambiguous | 0.5102 | ambiguous | -0.379 | Destabilizing | 0.99 | D | 0.755 | deleterious | None | None | None | None | N |
| D/L | 0.4464 | ambiguous | 0.4342 | ambiguous | 0.368 | Stabilizing | 0.995 | D | 0.752 | deleterious | None | None | None | None | N |
| D/M | 0.6814 | likely_pathogenic | 0.6614 | pathogenic | 0.708 | Stabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| D/N | 0.1401 | likely_benign | 0.1326 | benign | -0.625 | Destabilizing | 0.993 | D | 0.748 | deleterious | N | 0.483018259 | None | None | N |
| D/P | 0.8774 | likely_pathogenic | 0.8694 | pathogenic | 0.135 | Stabilizing | 0.998 | D | 0.766 | deleterious | None | None | None | None | N |
| D/Q | 0.4363 | ambiguous | 0.4104 | ambiguous | -0.53 | Destabilizing | 0.99 | D | 0.734 | prob.delet. | None | None | None | None | N |
| D/R | 0.6211 | likely_pathogenic | 0.6121 | pathogenic | -0.251 | Destabilizing | 0.995 | D | 0.773 | deleterious | None | None | None | None | N |
| D/S | 0.1323 | likely_benign | 0.1228 | benign | -0.832 | Destabilizing | 0.983 | D | 0.696 | prob.neutral | None | None | None | None | N |
| D/T | 0.3098 | likely_benign | 0.2888 | benign | -0.603 | Destabilizing | 0.995 | D | 0.737 | prob.delet. | None | None | None | None | N |
| D/V | 0.314 | likely_benign | 0.3022 | benign | 0.135 | Stabilizing | 0.997 | D | 0.743 | deleterious | N | 0.494881544 | None | None | N |
| D/W | 0.9432 | likely_pathogenic | 0.9412 | pathogenic | -0.165 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| D/Y | 0.3517 | ambiguous | 0.3561 | ambiguous | -0.055 | Destabilizing | 1.0 | D | 0.817 | deleterious | N | 0.495135033 | 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.