Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34307 | 103144;103145;103146 | chr2:178533696;178533695;178533694 | chr2:179398423;179398422;179398421 |
| N2AB | 32666 | 98221;98222;98223 | chr2:178533696;178533695;178533694 | chr2:179398423;179398422;179398421 |
| N2A | 31739 | 95440;95441;95442 | chr2:178533696;178533695;178533694 | chr2:179398423;179398422;179398421 |
| N2B | 25242 | 75949;75950;75951 | chr2:178533696;178533695;178533694 | chr2:179398423;179398422;179398421 |
| Novex-1 | 25367 | 76324;76325;76326 | chr2:178533696;178533695;178533694 | chr2:179398423;179398422;179398421 |
| Novex-2 | 25434 | 76525;76526;76527 | chr2:178533696;178533695;178533694 | chr2:179398423;179398422;179398421 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | None | None | 1.0 | D | 0.871 | 0.626 | 0.781510581047 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/N | rs769306235  |
-2.769 | 1.0 | D | 0.884 | 0.658 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| Y/N | rs769306235 |
-2.769 | 1.0 | D | 0.884 | 0.658 | None | gnomAD-4.0.0 | 1.84726E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.33846E-05 | 0 | 1.65645E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9691 | likely_pathogenic | 0.9677 | pathogenic | -2.992 | Highly Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| Y/C | 0.7123 | likely_pathogenic | 0.6763 | pathogenic | -2.253 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.528755056 | None | None | N |
| Y/D | 0.9578 | likely_pathogenic | 0.962 | pathogenic | -2.813 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | D | 0.55213923 | None | None | N |
| Y/E | 0.9827 | likely_pathogenic | 0.9824 | pathogenic | -2.606 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| Y/F | 0.2356 | likely_benign | 0.2119 | benign | -1.198 | Destabilizing | 0.999 | D | 0.499 | neutral | D | 0.523573269 | None | None | N |
| Y/G | 0.96 | likely_pathogenic | 0.9579 | pathogenic | -3.434 | Highly Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| Y/H | 0.8094 | likely_pathogenic | 0.82 | pathogenic | -2.066 | Highly Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.495558286 | None | None | N |
| Y/I | 0.8242 | likely_pathogenic | 0.7936 | pathogenic | -1.545 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| Y/K | 0.9856 | likely_pathogenic | 0.9846 | pathogenic | -2.275 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| Y/L | 0.8173 | likely_pathogenic | 0.8065 | pathogenic | -1.545 | Destabilizing | 0.999 | D | 0.658 | neutral | None | None | None | None | N |
| Y/M | 0.9213 | likely_pathogenic | 0.911 | pathogenic | -1.48 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| Y/N | 0.8301 | likely_pathogenic | 0.8495 | pathogenic | -3.023 | Highly Destabilizing | 1.0 | D | 0.884 | deleterious | D | 0.540529435 | None | None | N |
| Y/P | 0.9912 | likely_pathogenic | 0.9907 | pathogenic | -2.039 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | N |
| Y/Q | 0.9776 | likely_pathogenic | 0.9778 | pathogenic | -2.729 | Highly Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| Y/R | 0.9641 | likely_pathogenic | 0.9604 | pathogenic | -2.069 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| Y/S | 0.9323 | likely_pathogenic | 0.9347 | pathogenic | -3.53 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | N | 0.519031365 | None | None | N |
| Y/T | 0.9525 | likely_pathogenic | 0.9549 | pathogenic | -3.19 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| Y/V | 0.7833 | likely_pathogenic | 0.7604 | pathogenic | -2.039 | Highly Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| Y/W | 0.76 | likely_pathogenic | 0.7236 | pathogenic | -0.535 | Destabilizing | 1.0 | D | 0.706 | prob.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.