Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26409 | 79450;79451;79452 | chr2:178566907;178566906;178566905 | chr2:179431634;179431633;179431632 |
| N2AB | 24768 | 74527;74528;74529 | chr2:178566907;178566906;178566905 | chr2:179431634;179431633;179431632 |
| N2A | 23841 | 71746;71747;71748 | chr2:178566907;178566906;178566905 | chr2:179431634;179431633;179431632 |
| N2B | 17344 | 52255;52256;52257 | chr2:178566907;178566906;178566905 | chr2:179431634;179431633;179431632 |
| Novex-1 | 17469 | 52630;52631;52632 | chr2:178566907;178566906;178566905 | chr2:179431634;179431633;179431632 |
| Novex-2 | 17536 | 52831;52832;52833 | chr2:178566907;178566906;178566905 | chr2:179431634;179431633;179431632 |
| 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/C | rs748258568  |
-0.466 | 0.999 | N | 0.709 | 0.402 | 0.66441189913 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 6.47E-05 | 2.9E-05 | None | 0 | 0 | None | 1.30719E-04 | None | 0 | 0 | 0 |
| R/C | rs748258568 |
-0.466 | 0.999 | N | 0.709 | 0.402 | 0.66441189913 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs748258568 |
-0.466 | 0.999 | N | 0.709 | 0.402 | 0.66441189913 | gnomAD-4.0.0 | 1.3636E-05 | None | None | None | None | N | None | 2.67158E-05 | 1.66789E-05 | None | 0 | 0 | None | 0 | 0 | 3.39078E-06 | 1.64716E-04 | 0 |
| R/H | rs72648206 |
-1.254 | 1.0 | N | 0.643 | 0.355 | None | gnomAD-2.1.1 | 5.68739E-04 | None | None | None | None | N | None | 2.07056E-04 | 1.13231E-04 | None | 2.90473E-04 | 2.57017E-04 | None | 3.92157E-04 | None | 0 | 9.95516E-04 | 4.21704E-04 |
| R/H | rs72648206 |
-1.254 | 1.0 | N | 0.643 | 0.355 | None | gnomAD-3.1.2 | 6.7062E-04 | None | None | None | None | N | None | 1.68935E-04 | 1.96721E-04 | 0 | 0 | 3.86698E-04 | None | 0 | 0 | 1.294E-03 | 2.07297E-04 | 4.77555E-04 |
| R/H | rs72648206 |
-1.254 | 1.0 | N | 0.643 | 0.355 | None | gnomAD-4.0.0 | 8.57715E-04 | None | None | None | None | N | None | 1.73315E-04 | 1.33387E-04 | None | 6.75767E-05 | 1.33881E-04 | None | 0 | 1.65017E-04 | 1.09267E-03 | 3.95283E-04 | 4.64253E-04 |
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 | 0.7261 | likely_pathogenic | 0.7576 | pathogenic | -0.539 | Destabilizing | 0.033 | N | 0.375 | neutral | None | None | None | None | N |
| R/C | 0.3414 | ambiguous | 0.3817 | ambiguous | -0.781 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | N | 0.495335616 | None | None | N |
| R/D | 0.9336 | likely_pathogenic | 0.9464 | pathogenic | -0.888 | Destabilizing | 0.987 | D | 0.696 | prob.neutral | None | None | None | None | N |
| R/E | 0.7234 | likely_pathogenic | 0.7618 | pathogenic | -0.735 | Destabilizing | 0.916 | D | 0.606 | neutral | None | None | None | None | N |
| R/F | 0.8394 | likely_pathogenic | 0.8602 | pathogenic | -0.364 | Destabilizing | 0.987 | D | 0.713 | prob.delet. | None | None | None | None | N |
| R/G | 0.6781 | likely_pathogenic | 0.7149 | pathogenic | -0.808 | Destabilizing | 0.913 | D | 0.593 | neutral | N | 0.466088866 | None | None | N |
| R/H | 0.1884 | likely_benign | 0.2152 | benign | -1.434 | Destabilizing | 1.0 | D | 0.643 | neutral | N | 0.472596552 | None | None | N |
| R/I | 0.623 | likely_pathogenic | 0.69 | pathogenic | 0.187 | Stabilizing | 0.975 | D | 0.713 | prob.delet. | None | None | None | None | N |
| R/K | 0.2024 | likely_benign | 0.2401 | benign | -0.548 | Destabilizing | 0.818 | D | 0.587 | neutral | None | None | None | None | N |
| R/L | 0.539 | ambiguous | 0.6125 | pathogenic | 0.187 | Stabilizing | 0.913 | D | 0.597 | neutral | N | 0.517537439 | None | None | N |
| R/M | 0.6696 | likely_pathogenic | 0.7346 | pathogenic | -0.491 | Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | N |
| R/N | 0.8879 | likely_pathogenic | 0.9139 | pathogenic | -0.727 | Destabilizing | 0.987 | D | 0.627 | neutral | None | None | None | None | N |
| R/P | 0.5923 | likely_pathogenic | 0.6147 | pathogenic | -0.037 | Destabilizing | 0.993 | D | 0.709 | prob.delet. | N | 0.441167237 | None | None | N |
| R/Q | 0.2178 | likely_benign | 0.2583 | benign | -0.606 | Destabilizing | 0.987 | D | 0.627 | neutral | None | None | None | None | N |
| R/S | 0.8336 | likely_pathogenic | 0.866 | pathogenic | -0.985 | Destabilizing | 0.913 | D | 0.613 | neutral | N | 0.465986734 | None | None | N |
| R/T | 0.7093 | likely_pathogenic | 0.7809 | pathogenic | -0.656 | Destabilizing | 0.916 | D | 0.637 | neutral | None | None | None | None | N |
| R/V | 0.68 | likely_pathogenic | 0.7365 | pathogenic | -0.037 | Destabilizing | 0.95 | D | 0.629 | neutral | None | None | None | None | N |
| R/W | 0.4138 | ambiguous | 0.4499 | ambiguous | -0.361 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/Y | 0.6576 | likely_pathogenic | 0.6814 | pathogenic | -0.068 | Destabilizing | 0.996 | D | 0.713 | 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.