Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26639 | 80140;80141;80142 | chr2:178566217;178566216;178566215 | chr2:179430944;179430943;179430942 |
| N2AB | 24998 | 75217;75218;75219 | chr2:178566217;178566216;178566215 | chr2:179430944;179430943;179430942 |
| N2A | 24071 | 72436;72437;72438 | chr2:178566217;178566216;178566215 | chr2:179430944;179430943;179430942 |
| N2B | 17574 | 52945;52946;52947 | chr2:178566217;178566216;178566215 | chr2:179430944;179430943;179430942 |
| Novex-1 | 17699 | 53320;53321;53322 | chr2:178566217;178566216;178566215 | chr2:179430944;179430943;179430942 |
| Novex-2 | 17766 | 53521;53522;53523 | chr2:178566217;178566216;178566215 | chr2:179430944;179430943;179430942 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs771730962  |
-2.123 | 0.008 | N | 0.288 | 0.376 | 0.553710877737 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs771730962 |
-2.123 | 0.008 | N | 0.288 | 0.376 | 0.553710877737 | gnomAD-4.0.0 | 4.10547E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 7.56086E-05 | None | 0 | 0 | 2.69855E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3168 | likely_benign | 0.2499 | benign | -2.108 | Highly Destabilizing | 0.415 | N | 0.43 | neutral | None | None | None | None | N |
| I/C | 0.7566 | likely_pathogenic | 0.7129 | pathogenic | -1.325 | Destabilizing | 0.989 | D | 0.538 | neutral | None | None | None | None | N |
| I/D | 0.8802 | likely_pathogenic | 0.8177 | pathogenic | -1.878 | Destabilizing | 0.923 | D | 0.632 | neutral | None | None | None | None | N |
| I/E | 0.6674 | likely_pathogenic | 0.5688 | pathogenic | -1.751 | Destabilizing | 0.923 | D | 0.635 | neutral | None | None | None | None | N |
| I/F | 0.2441 | likely_benign | 0.2083 | benign | -1.289 | Destabilizing | 0.901 | D | 0.449 | neutral | N | 0.510068143 | None | None | N |
| I/G | 0.7893 | likely_pathogenic | 0.7169 | pathogenic | -2.549 | Highly Destabilizing | 0.923 | D | 0.613 | neutral | None | None | None | None | N |
| I/H | 0.7267 | likely_pathogenic | 0.6474 | pathogenic | -1.7 | Destabilizing | 0.996 | D | 0.679 | prob.neutral | None | None | None | None | N |
| I/K | 0.5035 | ambiguous | 0.4396 | ambiguous | -1.586 | Destabilizing | 0.923 | D | 0.637 | neutral | None | None | None | None | N |
| I/L | 0.1393 | likely_benign | 0.1329 | benign | -0.895 | Destabilizing | 0.19 | N | 0.313 | neutral | D | 0.523381268 | None | None | N |
| I/M | 0.092 | likely_benign | 0.0847 | benign | -0.751 | Destabilizing | 0.901 | D | 0.48 | neutral | N | 0.509054185 | None | None | N |
| I/N | 0.5356 | ambiguous | 0.4318 | ambiguous | -1.651 | Destabilizing | 0.901 | D | 0.659 | neutral | D | 0.552659435 | None | None | N |
| I/P | 0.8452 | likely_pathogenic | 0.7735 | pathogenic | -1.274 | Destabilizing | 0.961 | D | 0.656 | neutral | None | None | None | None | N |
| I/Q | 0.5488 | ambiguous | 0.457 | ambiguous | -1.67 | Destabilizing | 0.961 | D | 0.675 | prob.neutral | None | None | None | None | N |
| I/R | 0.4071 | ambiguous | 0.3476 | ambiguous | -1.104 | Destabilizing | 0.923 | D | 0.665 | neutral | None | None | None | None | N |
| I/S | 0.4196 | ambiguous | 0.3309 | benign | -2.316 | Highly Destabilizing | 0.565 | D | 0.551 | neutral | N | 0.517665467 | None | None | N |
| I/T | 0.1551 | likely_benign | 0.1092 | benign | -2.052 | Highly Destabilizing | 0.008 | N | 0.288 | neutral | N | 0.521931428 | None | None | N |
| I/V | 0.084 | likely_benign | 0.0814 | benign | -1.274 | Destabilizing | 0.003 | N | 0.129 | neutral | N | 0.500328263 | None | None | N |
| I/W | 0.7479 | likely_pathogenic | 0.7191 | pathogenic | -1.483 | Destabilizing | 0.996 | D | 0.706 | prob.neutral | None | None | None | None | N |
| I/Y | 0.6205 | likely_pathogenic | 0.5692 | pathogenic | -1.227 | Destabilizing | 0.961 | D | 0.535 | neutral | 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.