Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21826 | 65701;65702;65703 | chr2:178583706;178583705;178583704 | chr2:179448433;179448432;179448431 |
| N2AB | 20185 | 60778;60779;60780 | chr2:178583706;178583705;178583704 | chr2:179448433;179448432;179448431 |
| N2A | 19258 | 57997;57998;57999 | chr2:178583706;178583705;178583704 | chr2:179448433;179448432;179448431 |
| N2B | 12761 | 38506;38507;38508 | chr2:178583706;178583705;178583704 | chr2:179448433;179448432;179448431 |
| Novex-1 | 12886 | 38881;38882;38883 | chr2:178583706;178583705;178583704 | chr2:179448433;179448432;179448431 |
| Novex-2 | 12953 | 39082;39083;39084 | chr2:178583706;178583705;178583704 | chr2:179448433;179448432;179448431 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | rs763824247  |
-0.65 | 0.999 | N | 0.683 | 0.325 | 0.460526725402 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| E/K | rs763824247 |
-0.65 | 0.999 | N | 0.683 | 0.325 | 0.460526725402 | gnomAD-4.0.0 | 3.18899E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72505E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.264 | likely_benign | 0.2499 | benign | -0.665 | Destabilizing | 0.999 | D | 0.667 | neutral | N | 0.471240199 | None | None | N |
| E/C | 0.9471 | likely_pathogenic | 0.9352 | pathogenic | -0.34 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| E/D | 0.2578 | likely_benign | 0.2468 | benign | -0.662 | Destabilizing | 0.999 | D | 0.553 | neutral | N | 0.51775087 | None | None | N |
| E/F | 0.9345 | likely_pathogenic | 0.9195 | pathogenic | -0.179 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | N |
| E/G | 0.2706 | likely_benign | 0.2636 | benign | -0.957 | Destabilizing | 1.0 | D | 0.632 | neutral | N | 0.495121807 | None | None | N |
| E/H | 0.8297 | likely_pathogenic | 0.8023 | pathogenic | -0.158 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | N |
| E/I | 0.6253 | likely_pathogenic | 0.5758 | pathogenic | 0.107 | Stabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | N |
| E/K | 0.3448 | ambiguous | 0.3201 | benign | -0.083 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | N | 0.476902193 | None | None | N |
| E/L | 0.6536 | likely_pathogenic | 0.6278 | pathogenic | 0.107 | Stabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| E/M | 0.6903 | likely_pathogenic | 0.6624 | pathogenic | 0.284 | Stabilizing | 1.0 | D | 0.587 | neutral | None | None | None | None | N |
| E/N | 0.484 | ambiguous | 0.4507 | ambiguous | -0.595 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| E/P | 0.4549 | ambiguous | 0.4914 | ambiguous | -0.13 | Destabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| E/Q | 0.28 | likely_benign | 0.2523 | benign | -0.508 | Destabilizing | 1.0 | D | 0.673 | neutral | N | 0.477155683 | None | None | N |
| E/R | 0.5402 | ambiguous | 0.5089 | ambiguous | 0.224 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| E/S | 0.4218 | ambiguous | 0.3912 | ambiguous | -0.804 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| E/T | 0.4716 | ambiguous | 0.4382 | ambiguous | -0.56 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| E/V | 0.4033 | ambiguous | 0.3711 | ambiguous | -0.13 | Destabilizing | 1.0 | D | 0.633 | neutral | N | 0.494868317 | None | None | N |
| E/W | 0.9712 | likely_pathogenic | 0.9679 | pathogenic | 0.096 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| E/Y | 0.8719 | likely_pathogenic | 0.8466 | pathogenic | 0.087 | Stabilizing | 1.0 | D | 0.601 | 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.