Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15091 | 45496;45497;45498 | chr2:178621553;178621552;178621551 | chr2:179486280;179486279;179486278 |
| N2AB | 13450 | 40573;40574;40575 | chr2:178621553;178621552;178621551 | chr2:179486280;179486279;179486278 |
| N2A | 12523 | 37792;37793;37794 | chr2:178621553;178621552;178621551 | chr2:179486280;179486279;179486278 |
| N2B | 6026 | 18301;18302;18303 | chr2:178621553;178621552;178621551 | chr2:179486280;179486279;179486278 |
| Novex-1 | 6151 | 18676;18677;18678 | chr2:178621553;178621552;178621551 | chr2:179486280;179486279;179486278 |
| Novex-2 | 6218 | 18877;18878;18879 | chr2:178621553;178621552;178621551 | chr2:179486280;179486279;179486278 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs776532148  |
-0.706 | 0.005 | N | 0.095 | 0.323 | 0.276065633971 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.62E-05 | None | 0 | None | 0 | 0 | 0 |
| N/D | rs776532148 |
-0.706 | 0.005 | N | 0.095 | 0.323 | 0.276065633971 | gnomAD-4.0.0 | 2.7387E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.01133E-04 | None | 0 | 0 | 0 | 0 | 0 |
| N/Y | rs776532148 |
-0.295 | 0.989 | D | 0.463 | 0.623 | 0.769302405176 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.3077E-04 | None | 0 | 0 | 0 |
| N/Y | rs776532148 |
-0.295 | 0.989 | D | 0.463 | 0.623 | 0.769302405176 | gnomAD-4.0.0 | 1.16395E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.97156E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3373 | likely_benign | 0.3247 | benign | -0.395 | Destabilizing | 0.525 | D | 0.35 | neutral | None | None | None | None | N |
| N/C | 0.543 | ambiguous | 0.5724 | pathogenic | 0.439 | Stabilizing | 0.998 | D | 0.495 | neutral | None | None | None | None | N |
| N/D | 0.1111 | likely_benign | 0.1055 | benign | -0.705 | Destabilizing | 0.005 | N | 0.095 | neutral | N | 0.470173653 | None | None | N |
| N/E | 0.3612 | ambiguous | 0.35 | ambiguous | -0.675 | Destabilizing | 0.525 | D | 0.261 | neutral | None | None | None | None | N |
| N/F | 0.6745 | likely_pathogenic | 0.6776 | pathogenic | -0.43 | Destabilizing | 0.991 | D | 0.471 | neutral | None | None | None | None | N |
| N/G | 0.2822 | likely_benign | 0.2832 | benign | -0.675 | Destabilizing | 0.002 | N | 0.088 | neutral | None | None | None | None | N |
| N/H | 0.1387 | likely_benign | 0.1365 | benign | -0.766 | Destabilizing | 0.989 | D | 0.368 | neutral | D | 0.546848159 | None | None | N |
| N/I | 0.5135 | ambiguous | 0.4906 | ambiguous | 0.285 | Stabilizing | 0.989 | D | 0.489 | neutral | D | 0.670443272 | None | None | N |
| N/K | 0.2902 | likely_benign | 0.2977 | benign | -0.212 | Destabilizing | 0.954 | D | 0.275 | neutral | D | 0.524379579 | None | None | N |
| N/L | 0.4439 | ambiguous | 0.4574 | ambiguous | 0.285 | Stabilizing | 0.974 | D | 0.461 | neutral | None | None | None | None | N |
| N/M | 0.4947 | ambiguous | 0.4812 | ambiguous | 0.884 | Stabilizing | 0.998 | D | 0.453 | neutral | None | None | None | None | N |
| N/P | 0.8954 | likely_pathogenic | 0.8794 | pathogenic | 0.088 | Stabilizing | 0.991 | D | 0.467 | neutral | None | None | None | None | N |
| N/Q | 0.3585 | ambiguous | 0.3549 | ambiguous | -0.726 | Destabilizing | 0.974 | D | 0.347 | neutral | None | None | None | None | N |
| N/R | 0.3768 | ambiguous | 0.4058 | ambiguous | -0.2 | Destabilizing | 0.974 | D | 0.349 | neutral | None | None | None | None | N |
| N/S | 0.1308 | likely_benign | 0.1258 | benign | -0.487 | Destabilizing | 0.625 | D | 0.323 | neutral | D | 0.542184633 | None | None | N |
| N/T | 0.2325 | likely_benign | 0.223 | benign | -0.305 | Destabilizing | 0.891 | D | 0.264 | neutral | D | 0.599792325 | None | None | N |
| N/V | 0.4927 | ambiguous | 0.4858 | ambiguous | 0.088 | Stabilizing | 0.974 | D | 0.467 | neutral | None | None | None | None | N |
| N/W | 0.8415 | likely_pathogenic | 0.852 | pathogenic | -0.352 | Destabilizing | 0.998 | D | 0.573 | neutral | None | None | None | None | N |
| N/Y | 0.1995 | likely_benign | 0.2211 | benign | -0.107 | Destabilizing | 0.989 | D | 0.463 | neutral | D | 0.631638836 | 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.