Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 999 | 3220;3221;3222 | chr2:178782911;178782910;178782909 | chr2:179647638;179647637;179647636 |
| N2AB | 999 | 3220;3221;3222 | chr2:178782911;178782910;178782909 | chr2:179647638;179647637;179647636 |
| N2A | 999 | 3220;3221;3222 | chr2:178782911;178782910;178782909 | chr2:179647638;179647637;179647636 |
| N2B | 953 | 3082;3083;3084 | chr2:178782911;178782910;178782909 | chr2:179647638;179647637;179647636 |
| Novex-1 | 953 | 3082;3083;3084 | chr2:178782911;178782910;178782909 | chr2:179647638;179647637;179647636 |
| Novex-2 | 953 | 3082;3083;3084 | chr2:178782911;178782910;178782909 | chr2:179647638;179647637;179647636 |
| Novex-3 | 999 | 3220;3221;3222 | chr2:178782911;178782910;178782909 | chr2:179647638;179647637;179647636 |
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/C | rs142000511  |
-0.975 | 1.0 | N | 0.764 | 0.629 | None | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | N | None | 1.23062E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| R/C | rs142000511 |
-0.975 | 1.0 | N | 0.764 | 0.629 | None | gnomAD-4.0.0 | 6.84079E-06 | None | None | None | None | N | None | 2.98704E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29513E-06 | 2.31863E-05 | 0 |
| R/H | None | -1.723 | 0.999 | N | 0.577 | 0.446 | None | gnomAD-2.1.1 | 2.83E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51155E-04 | None | 0 | None | 0 | 2.33E-05 | 0 |
| R/H | None | -1.723 | 0.999 | N | 0.577 | 0.446 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.85654E-04 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/H | None | -1.723 | 0.999 | N | 0.577 | 0.446 | None | gnomAD-4.0.0 | 1.98256E-05 | None | None | None | None | N | None | 1.33276E-05 | 0 | None | 0 | 1.78341E-04 | None | 0 | 0 | 1.77966E-05 | 2.19606E-05 | 0 |
| R/L | rs371757623 |
None | 0.996 | N | 0.653 | 0.443 | 0.667830379453 | gnomAD-4.0.0 | 1.36816E-06 | None | None | None | None | N | None | 2.98704E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99305E-07 | 0 | 0 |
| R/S | None | None | 0.831 | N | 0.439 | 0.498 | 0.348764635752 | gnomAD-4.0.0 | 6.8408E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15934E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7251 | likely_pathogenic | 0.8069 | pathogenic | -1.027 | Destabilizing | 0.931 | D | 0.597 | neutral | None | None | None | None | N |
| R/C | 0.2786 | likely_benign | 0.3404 | ambiguous | -0.979 | Destabilizing | 1.0 | D | 0.764 | deleterious | N | 0.476369239 | None | None | N |
| R/D | 0.9354 | likely_pathogenic | 0.9631 | pathogenic | -0.37 | Destabilizing | 0.985 | D | 0.668 | neutral | None | None | None | None | N |
| R/E | 0.5762 | likely_pathogenic | 0.6679 | pathogenic | -0.243 | Destabilizing | 0.971 | D | 0.523 | neutral | None | None | None | None | N |
| R/F | 0.846 | likely_pathogenic | 0.8923 | pathogenic | -0.808 | Destabilizing | 0.999 | D | 0.747 | deleterious | None | None | None | None | N |
| R/G | 0.6273 | likely_pathogenic | 0.7477 | pathogenic | -1.349 | Destabilizing | 0.992 | D | 0.631 | neutral | N | 0.504476239 | None | None | N |
| R/H | 0.1293 | likely_benign | 0.1538 | benign | -1.513 | Destabilizing | 0.999 | D | 0.577 | neutral | N | 0.503762505 | None | None | N |
| R/I | 0.5619 | ambiguous | 0.6357 | pathogenic | -0.15 | Destabilizing | 0.998 | D | 0.738 | prob.delet. | None | None | None | None | N |
| R/K | 0.1487 | likely_benign | 0.1591 | benign | -1.164 | Destabilizing | 0.931 | D | 0.535 | neutral | None | None | None | None | N |
| R/L | 0.508 | ambiguous | 0.599 | pathogenic | -0.15 | Destabilizing | 0.996 | D | 0.653 | neutral | N | 0.494036375 | None | None | N |
| R/M | 0.5576 | ambiguous | 0.6473 | pathogenic | -0.391 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/N | 0.8206 | likely_pathogenic | 0.8779 | pathogenic | -0.595 | Destabilizing | 0.985 | D | 0.532 | neutral | None | None | None | None | N |
| R/P | 0.9937 | likely_pathogenic | 0.9974 | pathogenic | -0.422 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | N | 0.506091663 | None | None | N |
| R/Q | 0.118 | likely_benign | 0.1355 | benign | -0.765 | Destabilizing | 0.856 | D | 0.438 | neutral | None | None | None | None | N |
| R/S | 0.6591 | likely_pathogenic | 0.7565 | pathogenic | -1.376 | Destabilizing | 0.831 | D | 0.439 | neutral | N | 0.400494959 | None | None | N |
| R/T | 0.3934 | ambiguous | 0.4882 | ambiguous | -1.069 | Destabilizing | 0.971 | D | 0.582 | neutral | None | None | None | None | N |
| R/V | 0.5872 | likely_pathogenic | 0.6512 | pathogenic | -0.422 | Destabilizing | 0.998 | D | 0.69 | prob.neutral | None | None | None | None | N |
| R/W | 0.418 | ambiguous | 0.5263 | ambiguous | -0.411 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| R/Y | 0.6723 | likely_pathogenic | 0.7571 | pathogenic | -0.132 | Destabilizing | 0.999 | D | 0.733 | 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.