Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26327 | 79204;79205;79206 | chr2:178567153;178567152;178567151 | chr2:179431880;179431879;179431878 |
| N2AB | 24686 | 74281;74282;74283 | chr2:178567153;178567152;178567151 | chr2:179431880;179431879;179431878 |
| N2A | 23759 | 71500;71501;71502 | chr2:178567153;178567152;178567151 | chr2:179431880;179431879;179431878 |
| N2B | 17262 | 52009;52010;52011 | chr2:178567153;178567152;178567151 | chr2:179431880;179431879;179431878 |
| Novex-1 | 17387 | 52384;52385;52386 | chr2:178567153;178567152;178567151 | chr2:179431880;179431879;179431878 |
| Novex-2 | 17454 | 52585;52586;52587 | chr2:178567153;178567152;178567151 | chr2:179431880;179431879;179431878 |
| 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/L | None | None | 0.913 | N | 0.608 | 0.51 | 0.592397689306 | gnomAD-4.0.0 | 6.8433E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15953E-05 | 0 |
| R/Q | rs370367786  |
-1.144 | 0.999 | N | 0.475 | 0.425 | None | gnomAD-2.1.1 | 3.94E-05 | None | None | None | None | N | None | 8.27E-05 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 6.28E-05 | 0 |
| R/Q | rs370367786 |
-1.144 | 0.999 | N | 0.475 | 0.425 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 1.20697E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 4.78469E-04 |
| R/Q | rs370367786 |
-1.144 | 0.999 | N | 0.475 | 0.425 | None | gnomAD-4.0.0 | 5.20647E-05 | None | None | None | None | N | None | 9.34929E-05 | 3.33478E-05 | None | 0 | 0 | None | 0 | 0 | 6.18852E-05 | 0 | 3.20297E-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 | 0.9935 | likely_pathogenic | 0.9919 | pathogenic | -2.014 | Highly Destabilizing | 0.845 | D | 0.534 | neutral | None | None | None | None | N |
| R/C | 0.8233 | likely_pathogenic | 0.7829 | pathogenic | -1.86 | Destabilizing | 0.073 | N | 0.495 | neutral | None | None | None | None | N |
| R/D | 0.9993 | likely_pathogenic | 0.9994 | pathogenic | -0.816 | Destabilizing | 0.996 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/E | 0.9892 | likely_pathogenic | 0.989 | pathogenic | -0.603 | Destabilizing | 0.985 | D | 0.449 | neutral | None | None | None | None | N |
| R/F | 0.9975 | likely_pathogenic | 0.9973 | pathogenic | -1.208 | Destabilizing | 0.987 | D | 0.791 | deleterious | None | None | None | None | N |
| R/G | 0.9869 | likely_pathogenic | 0.9857 | pathogenic | -2.36 | Highly Destabilizing | 0.977 | D | 0.631 | neutral | N | 0.511606674 | None | None | N |
| R/H | 0.9185 | likely_pathogenic | 0.9036 | pathogenic | -2.117 | Highly Destabilizing | 0.999 | D | 0.509 | neutral | None | None | None | None | N |
| R/I | 0.9929 | likely_pathogenic | 0.993 | pathogenic | -1.011 | Destabilizing | 0.975 | D | 0.78 | deleterious | None | None | None | None | N |
| R/K | 0.7383 | likely_pathogenic | 0.6888 | pathogenic | -1.302 | Destabilizing | 0.957 | D | 0.461 | neutral | None | None | None | None | N |
| R/L | 0.9806 | likely_pathogenic | 0.9774 | pathogenic | -1.011 | Destabilizing | 0.913 | D | 0.608 | neutral | N | 0.500477405 | None | None | N |
| R/M | 0.9838 | likely_pathogenic | 0.9812 | pathogenic | -1.503 | Destabilizing | 0.999 | D | 0.668 | neutral | None | None | None | None | N |
| R/N | 0.9978 | likely_pathogenic | 0.9973 | pathogenic | -1.205 | Destabilizing | 0.996 | D | 0.467 | neutral | None | None | None | None | N |
| R/P | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -1.335 | Destabilizing | 0.998 | D | 0.751 | deleterious | D | 0.546093664 | None | None | N |
| R/Q | 0.7777 | likely_pathogenic | 0.7464 | pathogenic | -1.12 | Destabilizing | 0.999 | D | 0.475 | neutral | N | 0.486181357 | None | None | N |
| R/S | 0.998 | likely_pathogenic | 0.9977 | pathogenic | -2.166 | Highly Destabilizing | 0.916 | D | 0.563 | neutral | None | None | None | None | N |
| R/T | 0.9959 | likely_pathogenic | 0.9957 | pathogenic | -1.742 | Destabilizing | 0.916 | D | 0.574 | neutral | None | None | None | None | N |
| R/V | 0.9918 | likely_pathogenic | 0.9908 | pathogenic | -1.335 | Destabilizing | 0.975 | D | 0.714 | prob.delet. | None | None | None | None | N |
| R/W | 0.9711 | likely_pathogenic | 0.9687 | pathogenic | -0.674 | Destabilizing | 0.999 | D | 0.732 | prob.delet. | None | None | None | None | N |
| R/Y | 0.9903 | likely_pathogenic | 0.9883 | pathogenic | -0.552 | Destabilizing | 0.996 | D | 0.757 | deleterious | 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.