Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28060 | 84403;84404;84405 | chr2:178561954;178561953;178561952 | chr2:179426681;179426680;179426679 |
| N2AB | 26419 | 79480;79481;79482 | chr2:178561954;178561953;178561952 | chr2:179426681;179426680;179426679 |
| N2A | 25492 | 76699;76700;76701 | chr2:178561954;178561953;178561952 | chr2:179426681;179426680;179426679 |
| N2B | 18995 | 57208;57209;57210 | chr2:178561954;178561953;178561952 | chr2:179426681;179426680;179426679 |
| Novex-1 | 19120 | 57583;57584;57585 | chr2:178561954;178561953;178561952 | chr2:179426681;179426680;179426679 |
| Novex-2 | 19187 | 57784;57785;57786 | chr2:178561954;178561953;178561952 | chr2:179426681;179426680;179426679 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/D | rs758626435  |
-1.546 | 0.822 | N | 0.757 | 0.267 | 0.320256813643 | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| G/D | rs758626435 |
-1.546 | 0.822 | N | 0.757 | 0.267 | 0.320256813643 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 1.44823E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| G/D | rs758626435 |
-1.546 | 0.822 | N | 0.757 | 0.267 | 0.320256813643 | gnomAD-4.0.0 | 1.02573E-05 | None | None | None | None | N | None | 1.18447E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 2.3952E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.1441 | likely_benign | 0.1441 | benign | -0.782 | Destabilizing | 0.489 | N | 0.612 | neutral | N | 0.471622274 | None | None | N |
| G/C | 0.2314 | likely_benign | 0.2584 | benign | -0.946 | Destabilizing | 0.997 | D | 0.775 | deleterious | D | 0.523341373 | None | None | N |
| G/D | 0.4435 | ambiguous | 0.4775 | ambiguous | -1.977 | Destabilizing | 0.822 | D | 0.757 | deleterious | N | 0.493120344 | None | None | N |
| G/E | 0.3179 | likely_benign | 0.3258 | benign | -1.958 | Destabilizing | 0.86 | D | 0.765 | deleterious | None | None | None | None | N |
| G/F | 0.5993 | likely_pathogenic | 0.6039 | pathogenic | -0.964 | Destabilizing | 0.978 | D | 0.794 | deleterious | None | None | None | None | N |
| G/H | 0.5359 | ambiguous | 0.5701 | pathogenic | -1.766 | Destabilizing | 0.994 | D | 0.725 | prob.delet. | None | None | None | None | N |
| G/I | 0.3236 | likely_benign | 0.3246 | benign | -0.159 | Destabilizing | 0.956 | D | 0.799 | deleterious | None | None | None | None | N |
| G/K | 0.4703 | ambiguous | 0.4591 | ambiguous | -1.488 | Destabilizing | 0.754 | D | 0.76 | deleterious | None | None | None | None | N |
| G/L | 0.4356 | ambiguous | 0.4382 | ambiguous | -0.159 | Destabilizing | 0.754 | D | 0.795 | deleterious | None | None | None | None | N |
| G/M | 0.5005 | ambiguous | 0.5004 | ambiguous | -0.128 | Destabilizing | 0.998 | D | 0.781 | deleterious | None | None | None | None | N |
| G/N | 0.4628 | ambiguous | 0.4926 | ambiguous | -1.314 | Destabilizing | 0.86 | D | 0.699 | prob.neutral | None | None | None | None | N |
| G/P | 0.9173 | likely_pathogenic | 0.9055 | pathogenic | -0.325 | Destabilizing | 0.978 | D | 0.749 | deleterious | None | None | None | None | N |
| G/Q | 0.3986 | ambiguous | 0.4083 | ambiguous | -1.389 | Destabilizing | 0.956 | D | 0.755 | deleterious | None | None | None | None | N |
| G/R | 0.3794 | ambiguous | 0.3923 | ambiguous | -1.285 | Destabilizing | 0.032 | N | 0.55 | neutral | N | 0.48053259 | None | None | N |
| G/S | 0.1349 | likely_benign | 0.1422 | benign | -1.51 | Destabilizing | 0.153 | N | 0.327 | neutral | N | 0.477240907 | None | None | N |
| G/T | 0.2037 | likely_benign | 0.2196 | benign | -1.417 | Destabilizing | 0.076 | N | 0.574 | neutral | None | None | None | None | N |
| G/V | 0.2368 | likely_benign | 0.2501 | benign | -0.325 | Destabilizing | 0.89 | D | 0.786 | deleterious | N | 0.498640526 | None | None | N |
| G/W | 0.5807 | likely_pathogenic | 0.6135 | pathogenic | -1.566 | Destabilizing | 0.998 | D | 0.743 | deleterious | None | None | None | None | N |
| G/Y | 0.5182 | ambiguous | 0.5358 | ambiguous | -1.076 | Destabilizing | 0.993 | D | 0.787 | 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.