Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19754 | 59485;59486;59487 | chr2:178592859;178592858;178592857 | chr2:179457586;179457585;179457584 |
| N2AB | 18113 | 54562;54563;54564 | chr2:178592859;178592858;178592857 | chr2:179457586;179457585;179457584 |
| N2A | 17186 | 51781;51782;51783 | chr2:178592859;178592858;178592857 | chr2:179457586;179457585;179457584 |
| N2B | 10689 | 32290;32291;32292 | chr2:178592859;178592858;178592857 | chr2:179457586;179457585;179457584 |
| Novex-1 | 10814 | 32665;32666;32667 | chr2:178592859;178592858;178592857 | chr2:179457586;179457585;179457584 |
| Novex-2 | 10881 | 32866;32867;32868 | chr2:178592859;178592858;178592857 | chr2:179457586;179457585;179457584 |
| 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/E | rs752302911  |
-1.359 | 0.961 | N | 0.593 | 0.247 | 0.253726318573 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| K/E | rs752302911 |
-1.359 | 0.961 | N | 0.593 | 0.247 | 0.253726318573 | gnomAD-4.0.0 | 1.59184E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85945E-06 | 0 | 0 |
| K/N | None | None | 0.248 | N | 0.474 | 0.077 | 0.0986583533028 | gnomAD-4.0.0 | 6.84316E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65684E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.4067 | ambiguous | 0.4027 | ambiguous | -1.453 | Destabilizing | 0.97 | D | 0.567 | neutral | None | None | None | None | N |
| K/C | 0.4932 | ambiguous | 0.478 | ambiguous | -1.36 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| K/D | 0.6915 | likely_pathogenic | 0.6901 | pathogenic | -2.021 | Highly Destabilizing | 0.942 | D | 0.535 | neutral | None | None | None | None | N |
| K/E | 0.2668 | likely_benign | 0.2516 | benign | -1.712 | Destabilizing | 0.961 | D | 0.593 | neutral | N | 0.413908852 | None | None | N |
| K/F | 0.6487 | likely_pathogenic | 0.6551 | pathogenic | -0.57 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | N |
| K/G | 0.5964 | likely_pathogenic | 0.5938 | pathogenic | -1.929 | Destabilizing | 0.97 | D | 0.581 | neutral | None | None | None | None | N |
| K/H | 0.2094 | likely_benign | 0.2009 | benign | -1.832 | Destabilizing | 0.996 | D | 0.652 | neutral | None | None | None | None | N |
| K/I | 0.2505 | likely_benign | 0.2589 | benign | -0.087 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | N |
| K/L | 0.2536 | likely_benign | 0.258 | benign | -0.087 | Destabilizing | 0.97 | D | 0.572 | neutral | None | None | None | None | N |
| K/M | 0.19 | likely_benign | 0.1871 | benign | -0.495 | Destabilizing | 1.0 | D | 0.636 | neutral | N | 0.481483426 | None | None | N |
| K/N | 0.3934 | ambiguous | 0.3854 | ambiguous | -1.79 | Destabilizing | 0.248 | N | 0.474 | neutral | N | 0.452197882 | None | None | N |
| K/P | 0.9688 | likely_pathogenic | 0.97 | pathogenic | -0.525 | Destabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | N |
| K/Q | 0.1247 | likely_benign | 0.1195 | benign | -1.375 | Destabilizing | 0.961 | D | 0.581 | neutral | N | 0.397595393 | None | None | N |
| K/R | 0.0733 | likely_benign | 0.0722 | benign | -1.037 | Destabilizing | 0.031 | N | 0.304 | neutral | N | 0.431611966 | None | None | N |
| K/S | 0.4118 | ambiguous | 0.3917 | ambiguous | -2.251 | Highly Destabilizing | 0.97 | D | 0.566 | neutral | None | None | None | None | N |
| K/T | 0.1701 | likely_benign | 0.164 | benign | -1.698 | Destabilizing | 0.961 | D | 0.532 | neutral | N | 0.458257062 | None | None | N |
| K/V | 0.2374 | likely_benign | 0.2432 | benign | -0.525 | Destabilizing | 0.996 | D | 0.657 | neutral | None | None | None | None | N |
| K/W | 0.6565 | likely_pathogenic | 0.6556 | pathogenic | -0.71 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| K/Y | 0.4552 | ambiguous | 0.4458 | ambiguous | -0.365 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | 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.