Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33382 | 100369;100370;100371 | chr2:178536965;178536964;178536963 | chr2:179401692;179401691;179401690 |
| N2AB | 31741 | 95446;95447;95448 | chr2:178536965;178536964;178536963 | chr2:179401692;179401691;179401690 |
| N2A | 30814 | 92665;92666;92667 | chr2:178536965;178536964;178536963 | chr2:179401692;179401691;179401690 |
| N2B | 24317 | 73174;73175;73176 | chr2:178536965;178536964;178536963 | chr2:179401692;179401691;179401690 |
| Novex-1 | 24442 | 73549;73550;73551 | chr2:178536965;178536964;178536963 | chr2:179401692;179401691;179401690 |
| Novex-2 | 24509 | 73750;73751;73752 | chr2:178536965;178536964;178536963 | chr2:179401692;179401691;179401690 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs1212699230  |
0.068 | 0.999 | N | 0.647 | 0.389 | 0.634587441147 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 6.49E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/L | rs1212699230 |
0.068 | 0.999 | N | 0.647 | 0.389 | 0.634587441147 | gnomAD-4.0.0 | 6.84559E-07 | None | None | None | None | I | None | 2.99025E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1038 | likely_benign | 0.0977 | benign | -0.196 | Destabilizing | 0.994 | D | 0.386 | neutral | N | 0.458371706 | None | None | I |
| S/C | 0.2497 | likely_benign | 0.2037 | benign | -0.479 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| S/D | 0.3729 | ambiguous | 0.3916 | ambiguous | 0.4 | Stabilizing | 0.998 | D | 0.655 | prob.neutral | None | None | None | None | I |
| S/E | 0.468 | ambiguous | 0.484 | ambiguous | 0.323 | Stabilizing | 0.998 | D | 0.641 | neutral | None | None | None | None | I |
| S/F | 0.5257 | ambiguous | 0.3975 | ambiguous | -0.903 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | I |
| S/G | 0.1239 | likely_benign | 0.128 | benign | -0.272 | Destabilizing | 0.998 | D | 0.399 | neutral | None | None | None | None | I |
| S/H | 0.4617 | ambiguous | 0.4277 | ambiguous | -0.539 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| S/I | 0.5109 | ambiguous | 0.4558 | ambiguous | -0.125 | Destabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | I |
| S/K | 0.7005 | likely_pathogenic | 0.7056 | pathogenic | -0.255 | Destabilizing | 0.998 | D | 0.643 | neutral | None | None | None | None | I |
| S/L | 0.3058 | likely_benign | 0.2497 | benign | -0.125 | Destabilizing | 0.999 | D | 0.647 | neutral | N | 0.46721082 | None | None | I |
| S/M | 0.4135 | ambiguous | 0.3568 | ambiguous | -0.304 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| S/N | 0.1812 | likely_benign | 0.1849 | benign | -0.184 | Destabilizing | 0.998 | D | 0.645 | neutral | None | None | None | None | I |
| S/P | 0.4543 | ambiguous | 0.4702 | ambiguous | -0.122 | Destabilizing | 0.999 | D | 0.687 | prob.delet. | N | 0.491465559 | None | None | I |
| S/Q | 0.5096 | ambiguous | 0.5054 | ambiguous | -0.304 | Destabilizing | 0.999 | D | 0.671 | prob.neutral | None | None | None | None | I |
| S/R | 0.6753 | likely_pathogenic | 0.6734 | pathogenic | -0.073 | Destabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | I |
| S/T | 0.1204 | likely_benign | 0.1148 | benign | -0.26 | Destabilizing | 0.997 | D | 0.449 | neutral | N | 0.474493164 | None | None | I |
| S/V | 0.4027 | ambiguous | 0.3561 | ambiguous | -0.122 | Destabilizing | 0.999 | D | 0.675 | prob.neutral | None | None | None | None | I |
| S/W | 0.6831 | likely_pathogenic | 0.5905 | pathogenic | -1.005 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | I |
| S/Y | 0.4293 | ambiguous | 0.3435 | ambiguous | -0.658 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | I |
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.