Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25553 | 76882;76883;76884 | chr2:178569475;178569474;178569473 | chr2:179434202;179434201;179434200 |
| N2AB | 23912 | 71959;71960;71961 | chr2:178569475;178569474;178569473 | chr2:179434202;179434201;179434200 |
| N2A | 22985 | 69178;69179;69180 | chr2:178569475;178569474;178569473 | chr2:179434202;179434201;179434200 |
| N2B | 16488 | 49687;49688;49689 | chr2:178569475;178569474;178569473 | chr2:179434202;179434201;179434200 |
| Novex-1 | 16613 | 50062;50063;50064 | chr2:178569475;178569474;178569473 | chr2:179434202;179434201;179434200 |
| Novex-2 | 16680 | 50263;50264;50265 | chr2:178569475;178569474;178569473 | chr2:179434202;179434201;179434200 |
| 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 | rs1453473992  |
0.003 | None | N | 0.147 | 0.078 | 0.112648838833 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| D/G | rs1197063716 |
-0.391 | 0.166 | D | 0.302 | 0.355 | 0.233785782151 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.67001E-04 |
| D/G | rs1197063716 |
-0.391 | 0.166 | D | 0.302 | 0.355 | 0.233785782151 | gnomAD-4.0.0 | 3.18749E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43431E-05 | 3.02847E-05 |
| D/N | rs1246439715 |
0.063 | 0.491 | N | 0.218 | 0.211 | 0.235038932564 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs1246439715 |
0.063 | 0.491 | N | 0.218 | 0.211 | 0.235038932564 | gnomAD-4.0.0 | 1.59378E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78303E-05 | None | 0 | 0 | 0 | 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 | 0.1428 | likely_benign | 0.1594 | benign | 0.13 | Stabilizing | 0.166 | N | 0.329 | neutral | D | 0.523533197 | None | None | N |
| D/C | 0.5608 | ambiguous | 0.6024 | pathogenic | -0.076 | Destabilizing | 0.991 | D | 0.404 | neutral | None | None | None | None | N |
| D/E | 0.0839 | likely_benign | 0.0864 | benign | -0.367 | Destabilizing | None | N | 0.147 | neutral | N | 0.438741087 | None | None | N |
| D/F | 0.6358 | likely_pathogenic | 0.6771 | pathogenic | -0.044 | Destabilizing | 0.901 | D | 0.405 | neutral | None | None | None | None | N |
| D/G | 0.1228 | likely_benign | 0.1333 | benign | 0.035 | Stabilizing | 0.166 | N | 0.302 | neutral | D | 0.522149117 | None | None | N |
| D/H | 0.2669 | likely_benign | 0.2899 | benign | 0.565 | Stabilizing | 0.873 | D | 0.359 | neutral | N | 0.504481828 | None | None | N |
| D/I | 0.38 | ambiguous | 0.4186 | ambiguous | 0.307 | Stabilizing | 0.901 | D | 0.429 | neutral | None | None | None | None | N |
| D/K | 0.2411 | likely_benign | 0.2643 | benign | 0.481 | Stabilizing | 0.007 | N | 0.213 | neutral | None | None | None | None | N |
| D/L | 0.3646 | ambiguous | 0.3919 | ambiguous | 0.307 | Stabilizing | 0.561 | D | 0.395 | neutral | None | None | None | None | N |
| D/M | 0.5308 | ambiguous | 0.5674 | pathogenic | 0.081 | Stabilizing | 0.991 | D | 0.399 | neutral | None | None | None | None | N |
| D/N | 0.1017 | likely_benign | 0.1073 | benign | 0.309 | Stabilizing | 0.491 | N | 0.218 | neutral | N | 0.511758765 | None | None | N |
| D/P | 0.3208 | likely_benign | 0.3569 | ambiguous | 0.266 | Stabilizing | 0.722 | D | 0.374 | neutral | None | None | None | None | N |
| D/Q | 0.2447 | likely_benign | 0.2655 | benign | 0.29 | Stabilizing | 0.39 | N | 0.209 | neutral | None | None | None | None | N |
| D/R | 0.3383 | likely_benign | 0.3713 | ambiguous | 0.676 | Stabilizing | 0.39 | N | 0.367 | neutral | None | None | None | None | N |
| D/S | 0.1125 | likely_benign | 0.1206 | benign | 0.215 | Stabilizing | 0.017 | N | 0.156 | neutral | None | None | None | None | N |
| D/T | 0.1938 | likely_benign | 0.2145 | benign | 0.292 | Stabilizing | 0.39 | N | 0.314 | neutral | None | None | None | None | N |
| D/V | 0.219 | likely_benign | 0.2403 | benign | 0.266 | Stabilizing | 0.491 | N | 0.42 | neutral | N | 0.488579619 | None | None | N |
| D/W | 0.8503 | likely_pathogenic | 0.8729 | pathogenic | -0.045 | Destabilizing | 0.991 | D | 0.425 | neutral | None | None | None | None | N |
| D/Y | 0.2815 | likely_benign | 0.3016 | benign | 0.177 | Stabilizing | 0.954 | D | 0.403 | neutral | D | 0.527447928 | 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.