Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31364 | 94315;94316;94317 | chr2:178547536;178547535;178547534 | chr2:179412263;179412262;179412261 |
| N2AB | 29723 | 89392;89393;89394 | chr2:178547536;178547535;178547534 | chr2:179412263;179412262;179412261 |
| N2A | 28796 | 86611;86612;86613 | chr2:178547536;178547535;178547534 | chr2:179412263;179412262;179412261 |
| N2B | 22299 | 67120;67121;67122 | chr2:178547536;178547535;178547534 | chr2:179412263;179412262;179412261 |
| Novex-1 | 22424 | 67495;67496;67497 | chr2:178547536;178547535;178547534 | chr2:179412263;179412262;179412261 |
| Novex-2 | 22491 | 67696;67697;67698 | chr2:178547536;178547535;178547534 | chr2:179412263;179412262;179412261 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/R | rs377256863  |
-0.026 | 0.999 | N | 0.559 | 0.297 | None | gnomAD-2.1.1 | 4.83E-05 | None | None | None | None | N | None | 0 | 3.19211E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66113E-04 |
| K/R | rs377256863 |
-0.026 | 0.999 | N | 0.559 | 0.297 | None | gnomAD-3.1.2 | 5.91E-05 | None | None | None | None | N | None | 0 | 5.23766E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| K/R | rs377256863 |
-0.026 | 0.999 | N | 0.559 | 0.297 | None | gnomAD-4.0.0 | 2.30591E-05 | None | None | None | None | N | None | 0 | 2.88136E-04 | None | 0 | 0 | None | 0 | 0 | 2.39293E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.6949 | likely_pathogenic | 0.6799 | pathogenic | -0.17 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | N |
| K/C | 0.8604 | likely_pathogenic | 0.8439 | pathogenic | -0.385 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| K/D | 0.9322 | likely_pathogenic | 0.9121 | pathogenic | 0.19 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| K/E | 0.6079 | likely_pathogenic | 0.5491 | ambiguous | 0.228 | Stabilizing | 0.999 | D | 0.601 | neutral | N | 0.50212527 | None | None | N |
| K/F | 0.9553 | likely_pathogenic | 0.9487 | pathogenic | -0.237 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| K/G | 0.7803 | likely_pathogenic | 0.7416 | pathogenic | -0.416 | Destabilizing | 1.0 | D | 0.608 | neutral | None | None | None | None | N |
| K/H | 0.5978 | likely_pathogenic | 0.5708 | pathogenic | -0.684 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| K/I | 0.7093 | likely_pathogenic | 0.7266 | pathogenic | 0.411 | Stabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| K/L | 0.669 | likely_pathogenic | 0.6601 | pathogenic | 0.411 | Stabilizing | 1.0 | D | 0.608 | neutral | None | None | None | None | N |
| K/M | 0.5463 | ambiguous | 0.5388 | ambiguous | 0.171 | Stabilizing | 1.0 | D | 0.663 | neutral | N | 0.46948268 | None | None | N |
| K/N | 0.8244 | likely_pathogenic | 0.8013 | pathogenic | -0.005 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.4777469 | None | None | N |
| K/P | 0.831 | likely_pathogenic | 0.7981 | pathogenic | 0.247 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| K/Q | 0.2546 | likely_benign | 0.2393 | benign | -0.134 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.493428429 | None | None | N |
| K/R | 0.1027 | likely_benign | 0.1004 | benign | -0.209 | Destabilizing | 0.999 | D | 0.559 | neutral | N | 0.458374492 | None | None | N |
| K/S | 0.7491 | likely_pathogenic | 0.7324 | pathogenic | -0.57 | Destabilizing | 0.999 | D | 0.66 | neutral | None | None | None | None | N |
| K/T | 0.4114 | ambiguous | 0.4121 | ambiguous | -0.362 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.438476436 | None | None | N |
| K/V | 0.6648 | likely_pathogenic | 0.6785 | pathogenic | 0.247 | Stabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | N |
| K/W | 0.9267 | likely_pathogenic | 0.9046 | pathogenic | -0.198 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| K/Y | 0.9078 | likely_pathogenic | 0.8901 | pathogenic | 0.133 | Stabilizing | 1.0 | D | 0.647 | 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.