Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24509 | 73750;73751;73752 | chr2:178572607;178572606;178572605 | chr2:179437334;179437333;179437332 |
| N2AB | 22868 | 68827;68828;68829 | chr2:178572607;178572606;178572605 | chr2:179437334;179437333;179437332 |
| N2A | 21941 | 66046;66047;66048 | chr2:178572607;178572606;178572605 | chr2:179437334;179437333;179437332 |
| N2B | 15444 | 46555;46556;46557 | chr2:178572607;178572606;178572605 | chr2:179437334;179437333;179437332 |
| Novex-1 | 15569 | 46930;46931;46932 | chr2:178572607;178572606;178572605 | chr2:179437334;179437333;179437332 |
| Novex-2 | 15636 | 47131;47132;47133 | chr2:178572607;178572606;178572605 | chr2:179437334;179437333;179437332 |
| 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/P | None | None | 0.001 | N | 0.19 | 0.356 | 0.242825505644 | gnomAD-4.0.0 | 6.84405E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.5236E-05 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs745424387  |
0.022 | None | N | 0.101 | 0.051 | 0.158396225186 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| S/T | rs745424387 |
0.022 | None | N | 0.101 | 0.051 | 0.158396225186 | gnomAD-4.0.0 | 4.10643E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39771E-06 | 0 | 0 |
| S/Y | None | None | 0.773 | N | 0.461 | 0.524 | 0.66362909911 | gnomAD-4.0.0 | 1.59225E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85979E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1078 | likely_benign | 0.099 | benign | -0.258 | Destabilizing | 0.09 | N | 0.342 | neutral | N | 0.487885283 | None | None | I |
| S/C | 0.1575 | likely_benign | 0.1459 | benign | -0.295 | Destabilizing | 0.928 | D | 0.371 | neutral | N | 0.511055648 | None | None | I |
| S/D | 0.6243 | likely_pathogenic | 0.5902 | pathogenic | 0.355 | Stabilizing | 0.388 | N | 0.281 | neutral | None | None | None | None | I |
| S/E | 0.5625 | ambiguous | 0.5444 | ambiguous | 0.273 | Stabilizing | 0.388 | N | 0.291 | neutral | None | None | None | None | I |
| S/F | 0.3698 | ambiguous | 0.3268 | benign | -0.817 | Destabilizing | 0.773 | D | 0.476 | neutral | N | 0.502154878 | None | None | I |
| S/G | 0.2003 | likely_benign | 0.1771 | benign | -0.382 | Destabilizing | 0.207 | N | 0.304 | neutral | None | None | None | None | I |
| S/H | 0.4306 | ambiguous | 0.4075 | ambiguous | -0.863 | Destabilizing | 0.981 | D | 0.373 | neutral | None | None | None | None | I |
| S/I | 0.2906 | likely_benign | 0.2642 | benign | -0.064 | Destabilizing | 0.527 | D | 0.445 | neutral | None | None | None | None | I |
| S/K | 0.6991 | likely_pathogenic | 0.6628 | pathogenic | -0.41 | Destabilizing | 0.388 | N | 0.282 | neutral | None | None | None | None | I |
| S/L | 0.1597 | likely_benign | 0.1378 | benign | -0.064 | Destabilizing | 0.241 | N | 0.412 | neutral | None | None | None | None | I |
| S/M | 0.1908 | likely_benign | 0.1728 | benign | 0.021 | Stabilizing | 0.818 | D | 0.379 | neutral | None | None | None | None | I |
| S/N | 0.1972 | likely_benign | 0.1796 | benign | -0.19 | Destabilizing | 0.388 | N | 0.331 | neutral | None | None | None | None | I |
| S/P | 0.9023 | likely_pathogenic | 0.8553 | pathogenic | -0.099 | Destabilizing | 0.001 | N | 0.19 | neutral | N | 0.510548669 | None | None | I |
| S/Q | 0.4733 | ambiguous | 0.4628 | ambiguous | -0.374 | Destabilizing | 0.818 | D | 0.37 | neutral | None | None | None | None | I |
| S/R | 0.7136 | likely_pathogenic | 0.6644 | pathogenic | -0.262 | Destabilizing | 0.69 | D | 0.401 | neutral | None | None | None | None | I |
| S/T | 0.0691 | likely_benign | 0.0633 | benign | -0.28 | Destabilizing | None | N | 0.101 | neutral | N | 0.45138231 | None | None | I |
| S/V | 0.2415 | likely_benign | 0.2139 | benign | -0.099 | Destabilizing | 0.241 | N | 0.401 | neutral | None | None | None | None | I |
| S/W | 0.5782 | likely_pathogenic | 0.5307 | ambiguous | -0.859 | Destabilizing | 0.981 | D | 0.569 | neutral | None | None | None | None | I |
| S/Y | 0.3033 | likely_benign | 0.2746 | benign | -0.558 | Destabilizing | 0.773 | D | 0.461 | neutral | N | 0.499445853 | 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.