Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35974 | 108145;108146;108147 | chr2:178527068;178527067;178527066 | chr2:179391795;179391794;179391793 |
| N2AB | 34333 | 103222;103223;103224 | chr2:178527068;178527067;178527066 | chr2:179391795;179391794;179391793 |
| N2A | 33406 | 100441;100442;100443 | chr2:178527068;178527067;178527066 | chr2:179391795;179391794;179391793 |
| N2B | 26909 | 80950;80951;80952 | chr2:178527068;178527067;178527066 | chr2:179391795;179391794;179391793 |
| Novex-1 | 27034 | 81325;81326;81327 | chr2:178527068;178527067;178527066 | chr2:179391795;179391794;179391793 |
| Novex-2 | 27101 | 81526;81527;81528 | chr2:178527068;178527067;178527066 | chr2:179391795;179391794;179391793 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/R | rs372653064  |
-0.287 | 0.81 | N | 0.689 | 0.239 | 0.514015564596 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | -2.196(OBSL1) -1.611(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 2.80978E-04 |
| G/R | rs372653064 |
-0.287 | 0.81 | N | 0.689 | 0.239 | 0.514015564596 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | -2.196(OBSL1) -1.611(OBSCN) | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| G/R | rs372653064 |
-0.287 | 0.81 | N | 0.689 | 0.239 | 0.514015564596 | gnomAD-4.0.0 | 6.84188E-07 | None | None | None | -2.196(OBSL1) -1.611(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99431E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.1502 | likely_benign | 0.14 | benign | -0.784 | Destabilizing | 0.201 | N | 0.583 | neutral | N | 0.422272911 | None | -1.322(OBSL1) -0.723(OBSCN) | N |
| G/C | 0.249 | likely_benign | 0.254 | benign | -1.178 | Destabilizing | 0.992 | D | 0.667 | neutral | None | None | None | -2.005(OBSL1) -1.234(OBSCN) | N |
| G/D | 0.2799 | likely_benign | 0.2717 | benign | -1.206 | Destabilizing | 0.005 | N | 0.462 | neutral | None | None | None | -1.695(OBSL1) -1.38(OBSCN) | N |
| G/E | 0.1696 | likely_benign | 0.1567 | benign | -1.322 | Destabilizing | 0.004 | N | 0.539 | neutral | N | 0.393854159 | None | -1.772(OBSL1) -1.548(OBSCN) | N |
| G/F | 0.6697 | likely_pathogenic | 0.656 | pathogenic | -1.392 | Destabilizing | 0.972 | D | 0.689 | prob.neutral | None | None | None | -1.573(OBSL1) -0.572(OBSCN) | N |
| G/H | 0.3792 | ambiguous | 0.3642 | ambiguous | -1.117 | Destabilizing | 0.92 | D | 0.641 | neutral | None | None | None | -1.514(OBSL1) -0.266(OBSCN) | N |
| G/I | 0.3478 | ambiguous | 0.3265 | benign | -0.682 | Destabilizing | 0.92 | D | 0.71 | prob.delet. | None | None | None | -1.579(OBSL1) -1.08(OBSCN) | N |
| G/K | 0.3221 | likely_benign | 0.2986 | benign | -1.13 | Destabilizing | 0.447 | N | 0.671 | neutral | None | None | None | -2.273(OBSL1) -1.67(OBSCN) | N |
| G/L | 0.496 | ambiguous | 0.4727 | ambiguous | -0.682 | Destabilizing | 0.85 | D | 0.698 | prob.neutral | None | None | None | -1.579(OBSL1) -1.08(OBSCN) | N |
| G/M | 0.5291 | ambiguous | 0.5033 | ambiguous | -0.581 | Destabilizing | 0.992 | D | 0.66 | neutral | None | None | None | -1.633(OBSL1) -0.99(OBSCN) | N |
| G/N | 0.3543 | ambiguous | 0.3467 | ambiguous | -0.846 | Destabilizing | 0.447 | N | 0.631 | neutral | None | None | None | -1.83(OBSL1) -1.142(OBSCN) | N |
| G/P | 0.9793 | likely_pathogenic | 0.9786 | pathogenic | -0.68 | Destabilizing | 0.92 | D | 0.686 | prob.neutral | None | None | None | -1.492(OBSL1) -0.958(OBSCN) | N |
| G/Q | 0.2386 | likely_benign | 0.2206 | benign | -1.153 | Destabilizing | 0.127 | N | 0.555 | neutral | None | None | None | -1.924(OBSL1) -1.263(OBSCN) | N |
| G/R | 0.2102 | likely_benign | 0.1935 | benign | -0.71 | Destabilizing | 0.81 | D | 0.689 | prob.neutral | N | 0.404033867 | None | -2.196(OBSL1) -1.611(OBSCN) | N |
| G/S | 0.1072 | likely_benign | 0.1072 | benign | -1.054 | Destabilizing | 0.009 | N | 0.224 | neutral | None | None | None | -1.868(OBSL1) -0.844(OBSCN) | N |
| G/T | 0.1832 | likely_benign | 0.1743 | benign | -1.103 | Destabilizing | 0.447 | N | 0.668 | neutral | None | None | None | -1.964(OBSL1) -1.023(OBSCN) | N |
| G/V | 0.2473 | likely_benign | 0.2305 | benign | -0.68 | Destabilizing | 0.81 | D | 0.713 | prob.delet. | N | 0.389931206 | None | -1.492(OBSL1) -0.958(OBSCN) | N |
| G/W | 0.4473 | ambiguous | 0.4304 | ambiguous | -1.562 | Destabilizing | 0.99 | D | 0.667 | neutral | N | 0.473299165 | None | -1.724(OBSL1) -0.691(OBSCN) | N |
| G/Y | 0.5277 | ambiguous | 0.5095 | ambiguous | -1.203 | Destabilizing | 0.972 | D | 0.688 | prob.neutral | None | None | None | -1.587(OBSL1) -0.542(OBSCN) | 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.