Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24464 | 73615;73616;73617 | chr2:178572742;178572741;178572740 | chr2:179437469;179437468;179437467 |
| N2AB | 22823 | 68692;68693;68694 | chr2:178572742;178572741;178572740 | chr2:179437469;179437468;179437467 |
| N2A | 21896 | 65911;65912;65913 | chr2:178572742;178572741;178572740 | chr2:179437469;179437468;179437467 |
| N2B | 15399 | 46420;46421;46422 | chr2:178572742;178572741;178572740 | chr2:179437469;179437468;179437467 |
| Novex-1 | 15524 | 46795;46796;46797 | chr2:178572742;178572741;178572740 | chr2:179437469;179437468;179437467 |
| Novex-2 | 15591 | 46996;46997;46998 | chr2:178572742;178572741;178572740 | chr2:179437469;179437468;179437467 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs750056949  |
-0.253 | 0.994 | N | 0.561 | 0.301 | 0.202949470691 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | I | None | 1.93823E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| R/Q | rs750056949 |
-0.253 | 0.994 | N | 0.561 | 0.301 | 0.202949470691 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | I | None | 1.44949E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs750056949 |
-0.253 | 0.994 | N | 0.561 | 0.301 | 0.202949470691 | gnomAD-4.0.0 | 2.04546E-05 | None | None | None | None | I | None | 1.06889E-04 | 3.33411E-05 | None | 0 | 0 | None | 0 | 0 | 1.78027E-05 | 2.19616E-05 | 0 |
| R/W | rs369098292 |
-0.577 | 1.0 | N | 0.716 | 0.38 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/W | rs369098292 |
-0.577 | 1.0 | N | 0.716 | 0.38 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07727E-04 | 0 |
| R/W | rs369098292 |
-0.577 | 1.0 | N | 0.716 | 0.38 | None | gnomAD-4.0.0 | 1.0254E-05 | None | None | None | None | I | None | 1.69296E-05 | 0 | None | 0 | 2.42884E-05 | None | 0 | 0 | 0 | 4.02156E-05 | 8.53582E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7045 | likely_pathogenic | 0.7465 | pathogenic | -1.752 | Destabilizing | 0.845 | D | 0.55 | neutral | None | None | None | None | I |
| R/C | 0.3449 | ambiguous | 0.3748 | ambiguous | -1.793 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | I |
| R/D | 0.9197 | likely_pathogenic | 0.9349 | pathogenic | -0.726 | Destabilizing | 0.975 | D | 0.684 | prob.neutral | None | None | None | None | I |
| R/E | 0.6829 | likely_pathogenic | 0.7193 | pathogenic | -0.557 | Destabilizing | 0.845 | D | 0.519 | neutral | None | None | None | None | I |
| R/F | 0.7662 | likely_pathogenic | 0.8049 | pathogenic | -1.371 | Destabilizing | 0.996 | D | 0.723 | prob.delet. | None | None | None | None | I |
| R/G | 0.5766 | likely_pathogenic | 0.6253 | pathogenic | -2.087 | Highly Destabilizing | 0.954 | D | 0.604 | neutral | N | 0.484662603 | None | None | I |
| R/H | 0.2542 | likely_benign | 0.2662 | benign | -2.015 | Highly Destabilizing | 0.987 | D | 0.608 | neutral | None | None | None | None | I |
| R/I | 0.5398 | ambiguous | 0.5891 | pathogenic | -0.81 | Destabilizing | 0.987 | D | 0.727 | prob.delet. | None | None | None | None | I |
| R/K | 0.105 | likely_benign | 0.104 | benign | -1.528 | Destabilizing | 0.033 | N | 0.272 | neutral | None | None | None | None | I |
| R/L | 0.4271 | ambiguous | 0.4733 | ambiguous | -0.81 | Destabilizing | 0.954 | D | 0.604 | neutral | N | 0.499807322 | None | None | I |
| R/M | 0.4844 | ambiguous | 0.522 | ambiguous | -1.101 | Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | I |
| R/N | 0.8697 | likely_pathogenic | 0.8907 | pathogenic | -1.167 | Destabilizing | 0.975 | D | 0.559 | neutral | None | None | None | None | I |
| R/P | 0.8575 | likely_pathogenic | 0.8681 | pathogenic | -1.109 | Destabilizing | 0.993 | D | 0.716 | prob.delet. | N | 0.484916093 | None | None | I |
| R/Q | 0.2024 | likely_benign | 0.2165 | benign | -1.262 | Destabilizing | 0.994 | D | 0.561 | neutral | N | 0.472799319 | None | None | I |
| R/S | 0.8317 | likely_pathogenic | 0.8618 | pathogenic | -2.122 | Highly Destabilizing | 0.916 | D | 0.607 | neutral | None | None | None | None | I |
| R/T | 0.5977 | likely_pathogenic | 0.6488 | pathogenic | -1.747 | Destabilizing | 0.975 | D | 0.612 | neutral | None | None | None | None | I |
| R/V | 0.6002 | likely_pathogenic | 0.6501 | pathogenic | -1.109 | Destabilizing | 0.975 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/W | 0.395 | ambiguous | 0.4296 | ambiguous | -0.859 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | N | 0.473559787 | None | None | I |
| R/Y | 0.6746 | likely_pathogenic | 0.7173 | pathogenic | -0.638 | Destabilizing | 0.996 | D | 0.725 | 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.