Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24858 | 74797;74798;74799 | chr2:178571560;178571559;178571558 | chr2:179436287;179436286;179436285 |
| N2AB | 23217 | 69874;69875;69876 | chr2:178571560;178571559;178571558 | chr2:179436287;179436286;179436285 |
| N2A | 22290 | 67093;67094;67095 | chr2:178571560;178571559;178571558 | chr2:179436287;179436286;179436285 |
| N2B | 15793 | 47602;47603;47604 | chr2:178571560;178571559;178571558 | chr2:179436287;179436286;179436285 |
| Novex-1 | 15918 | 47977;47978;47979 | chr2:178571560;178571559;178571558 | chr2:179436287;179436286;179436285 |
| Novex-2 | 15985 | 48178;48179;48180 | chr2:178571560;178571559;178571558 | chr2:179436287;179436286;179436285 |
| 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 | rs1708197097  |
None | 0.822 | N | 0.629 | 0.258 | 0.575446509224 | gnomAD-4.0.0 | 2.7377E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69877E-06 | 1.15966E-05 | 0 |
| I/V | rs1191685615 |
-0.47 | 0.014 | N | 0.165 | 0.055 | 0.491455083755 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/V | rs1191685615 |
-0.47 | 0.014 | N | 0.165 | 0.055 | 0.491455083755 | gnomAD-4.0.0 | 3.18487E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86623E-05 | 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 | 0.317 | likely_benign | 0.312 | benign | -1.248 | Destabilizing | 0.559 | D | 0.592 | neutral | None | None | None | None | N |
| I/C | 0.6995 | likely_pathogenic | 0.6924 | pathogenic | -0.729 | Destabilizing | 0.998 | D | 0.715 | prob.delet. | None | None | None | None | N |
| I/D | 0.7797 | likely_pathogenic | 0.7745 | pathogenic | -0.732 | Destabilizing | 0.978 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/E | 0.6333 | likely_pathogenic | 0.6383 | pathogenic | -0.786 | Destabilizing | 0.978 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/F | 0.2962 | likely_benign | 0.2597 | benign | -0.964 | Destabilizing | 0.942 | D | 0.593 | neutral | N | 0.48234743 | None | None | N |
| I/G | 0.7473 | likely_pathogenic | 0.7389 | pathogenic | -1.501 | Destabilizing | 0.019 | N | 0.402 | neutral | None | None | None | None | N |
| I/H | 0.7011 | likely_pathogenic | 0.6675 | pathogenic | -0.692 | Destabilizing | 0.998 | D | 0.747 | deleterious | None | None | None | None | N |
| I/K | 0.5736 | likely_pathogenic | 0.5408 | ambiguous | -0.838 | Destabilizing | 0.978 | D | 0.738 | prob.delet. | None | None | None | None | N |
| I/L | 0.1257 | likely_benign | 0.1179 | benign | -0.662 | Destabilizing | 0.489 | N | 0.355 | neutral | N | 0.459547928 | None | None | N |
| I/M | 0.0872 | likely_benign | 0.081 | benign | -0.482 | Destabilizing | 0.97 | D | 0.595 | neutral | N | 0.437460503 | None | None | N |
| I/N | 0.336 | likely_benign | 0.3391 | benign | -0.58 | Destabilizing | 0.97 | D | 0.755 | deleterious | N | 0.436420353 | None | None | N |
| I/P | 0.503 | ambiguous | 0.504 | ambiguous | -0.824 | Destabilizing | 0.993 | D | 0.759 | deleterious | None | None | None | None | N |
| I/Q | 0.5668 | likely_pathogenic | 0.545 | ambiguous | -0.821 | Destabilizing | 0.993 | D | 0.753 | deleterious | None | None | None | None | N |
| I/R | 0.5193 | ambiguous | 0.4766 | ambiguous | -0.18 | Destabilizing | 0.978 | D | 0.759 | deleterious | None | None | None | None | N |
| I/S | 0.3725 | ambiguous | 0.3696 | ambiguous | -1.111 | Destabilizing | 0.942 | D | 0.648 | neutral | N | 0.470935571 | None | None | N |
| I/T | 0.155 | likely_benign | 0.1603 | benign | -1.057 | Destabilizing | 0.822 | D | 0.629 | neutral | N | 0.362383954 | None | None | N |
| I/V | 0.0802 | likely_benign | 0.0806 | benign | -0.824 | Destabilizing | 0.014 | N | 0.165 | neutral | N | 0.400691626 | None | None | N |
| I/W | 0.8516 | likely_pathogenic | 0.8147 | pathogenic | -0.984 | Destabilizing | 0.998 | D | 0.751 | deleterious | None | None | None | None | N |
| I/Y | 0.6482 | likely_pathogenic | 0.6182 | pathogenic | -0.773 | Destabilizing | 0.978 | D | 0.721 | prob.delet. | 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.