Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22369 | 67330;67331;67332 | chr2:178580182;178580181;178580180 | chr2:179444909;179444908;179444907 |
| N2AB | 20728 | 62407;62408;62409 | chr2:178580182;178580181;178580180 | chr2:179444909;179444908;179444907 |
| N2A | 19801 | 59626;59627;59628 | chr2:178580182;178580181;178580180 | chr2:179444909;179444908;179444907 |
| N2B | 13304 | 40135;40136;40137 | chr2:178580182;178580181;178580180 | chr2:179444909;179444908;179444907 |
| Novex-1 | 13429 | 40510;40511;40512 | chr2:178580182;178580181;178580180 | chr2:179444909;179444908;179444907 |
| Novex-2 | 13496 | 40711;40712;40713 | chr2:178580182;178580181;178580180 | chr2:179444909;179444908;179444907 |
| 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/N | None | None | 0.028 | N | 0.165 | 0.138 | 0.130388298395 | gnomAD-4.0.0 | 2.40066E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62501E-06 | 0 | 0 |
| D/V | rs759265517  |
0.195 | 0.684 | N | 0.403 | 0.333 | 0.552656131934 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| D/V | rs759265517 |
0.195 | 0.684 | N | 0.403 | 0.333 | 0.552656131934 | gnomAD-4.0.0 | 1.59272E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86053E-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 | 0.3331 | likely_benign | 0.2452 | benign | -0.309 | Destabilizing | 0.309 | N | 0.305 | neutral | N | 0.474130716 | None | None | N |
| D/C | 0.7486 | likely_pathogenic | 0.6332 | pathogenic | 0.206 | Stabilizing | 0.996 | D | 0.308 | neutral | None | None | None | None | N |
| D/E | 0.2073 | likely_benign | 0.157 | benign | -0.586 | Destabilizing | 0.028 | N | 0.099 | neutral | N | 0.461473513 | None | None | N |
| D/F | 0.674 | likely_pathogenic | 0.575 | pathogenic | -0.681 | Destabilizing | 0.984 | D | 0.329 | neutral | None | None | None | None | N |
| D/G | 0.2064 | likely_benign | 0.1747 | benign | -0.515 | Destabilizing | 0.003 | N | 0.13 | neutral | N | 0.499626469 | None | None | N |
| D/H | 0.4664 | ambiguous | 0.3416 | ambiguous | -0.941 | Destabilizing | 0.939 | D | 0.351 | neutral | N | 0.478739072 | None | None | N |
| D/I | 0.5721 | likely_pathogenic | 0.4453 | ambiguous | 0.184 | Stabilizing | 0.91 | D | 0.372 | neutral | None | None | None | None | N |
| D/K | 0.629 | likely_pathogenic | 0.4955 | ambiguous | 0.182 | Stabilizing | 0.742 | D | 0.352 | neutral | None | None | None | None | N |
| D/L | 0.5603 | ambiguous | 0.4526 | ambiguous | 0.184 | Stabilizing | 0.742 | D | 0.405 | neutral | None | None | None | None | N |
| D/M | 0.7291 | likely_pathogenic | 0.6227 | pathogenic | 0.632 | Stabilizing | 0.996 | D | 0.31 | neutral | None | None | None | None | N |
| D/N | 0.1223 | likely_benign | 0.1078 | benign | 0.007 | Stabilizing | 0.028 | N | 0.165 | neutral | N | 0.488483969 | None | None | N |
| D/P | 0.9649 | likely_pathogenic | 0.9367 | pathogenic | 0.042 | Stabilizing | 0.953 | D | 0.382 | neutral | None | None | None | None | N |
| D/Q | 0.5111 | ambiguous | 0.377 | ambiguous | 0.002 | Stabilizing | 0.91 | D | 0.323 | neutral | None | None | None | None | N |
| D/R | 0.6865 | likely_pathogenic | 0.5467 | ambiguous | 0.066 | Stabilizing | 0.91 | D | 0.364 | neutral | None | None | None | None | N |
| D/S | 0.2005 | likely_benign | 0.1565 | benign | -0.125 | Destabilizing | 0.101 | N | 0.101 | neutral | None | None | None | None | N |
| D/T | 0.2626 | likely_benign | 0.2001 | benign | 0.032 | Stabilizing | 0.037 | N | 0.157 | neutral | None | None | None | None | N |
| D/V | 0.3759 | ambiguous | 0.2758 | benign | 0.042 | Stabilizing | 0.684 | D | 0.403 | neutral | N | 0.504503103 | None | None | N |
| D/W | 0.9279 | likely_pathogenic | 0.885 | pathogenic | -0.694 | Destabilizing | 0.996 | D | 0.465 | neutral | None | None | None | None | N |
| D/Y | 0.2813 | likely_benign | 0.2259 | benign | -0.475 | Destabilizing | 0.979 | D | 0.327 | neutral | N | 0.515770503 | 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.