Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31365 | 94318;94319;94320 | chr2:178547533;178547532;178547531 | chr2:179412260;179412259;179412258 |
| N2AB | 29724 | 89395;89396;89397 | chr2:178547533;178547532;178547531 | chr2:179412260;179412259;179412258 |
| N2A | 28797 | 86614;86615;86616 | chr2:178547533;178547532;178547531 | chr2:179412260;179412259;179412258 |
| N2B | 22300 | 67123;67124;67125 | chr2:178547533;178547532;178547531 | chr2:179412260;179412259;179412258 |
| Novex-1 | 22425 | 67498;67499;67500 | chr2:178547533;178547532;178547531 | chr2:179412260;179412259;179412258 |
| Novex-2 | 22492 | 67699;67700;67701 | chr2:178547533;178547532;178547531 | chr2:179412260;179412259;179412258 |
| 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 | rs372593328  |
-0.178 | 1.0 | N | 0.732 | 0.394 | None | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | N | None | 1.65426E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| R/C | rs372593328 |
-0.178 | 1.0 | N | 0.732 | 0.394 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 9.66E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| R/C | rs372593328 |
-0.178 | 1.0 | N | 0.732 | 0.394 | None | gnomAD-4.0.0 | 1.23949E-05 | None | None | None | None | N | None | 8.01239E-05 | 1.6675E-05 | None | 0 | 2.23075E-05 | None | 0 | 0 | 8.47626E-06 | 0 | 3.20256E-05 |
| R/H | rs577262832 |
-0.69 | 1.0 | N | 0.778 | 0.346 | 0.377451072189 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 1.78E-05 | 1.66223E-04 |
| R/H | rs577262832 |
-0.69 | 1.0 | N | 0.778 | 0.346 | 0.377451072189 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs577262832 |
-0.69 | 1.0 | N | 0.778 | 0.346 | 0.377451072189 | gnomAD-4.0.0 | 3.40871E-05 | None | None | None | None | N | None | 1.33558E-05 | 0 | None | 0 | 4.4615E-05 | None | 0 | 3.28839E-04 | 3.89905E-05 | 3.29417E-05 | 1.60138E-05 |
| R/L | rs577262832 |
0.618 | 1.0 | N | 0.594 | 0.361 | 0.391470661076 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/L | rs577262832 |
0.618 | 1.0 | N | 0.594 | 0.361 | 0.391470661076 | gnomAD-4.0.0 | 1.36852E-06 | None | None | None | None | N | None | 0 | 2.23674E-05 | None | 0 | 0 | None | 0 | 0 | 8.99473E-07 | 0 | 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 | 0.7574 | likely_pathogenic | 0.6695 | pathogenic | 0.114 | Stabilizing | 0.999 | D | 0.606 | neutral | None | None | None | None | N |
| R/C | 0.3113 | likely_benign | 0.2874 | benign | -0.136 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | N | 0.481181381 | None | None | N |
| R/D | 0.8351 | likely_pathogenic | 0.769 | pathogenic | -0.189 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| R/E | 0.6486 | likely_pathogenic | 0.59 | pathogenic | -0.124 | Destabilizing | 0.999 | D | 0.651 | neutral | None | None | None | None | N |
| R/F | 0.8481 | likely_pathogenic | 0.8082 | pathogenic | -0.08 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| R/G | 0.4498 | ambiguous | 0.3444 | ambiguous | -0.074 | Destabilizing | 1.0 | D | 0.594 | neutral | N | 0.486542529 | None | None | N |
| R/H | 0.166 | likely_benign | 0.1475 | benign | -0.56 | Destabilizing | 1.0 | D | 0.778 | deleterious | N | 0.466582618 | None | None | N |
| R/I | 0.7492 | likely_pathogenic | 0.6925 | pathogenic | 0.573 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/K | 0.1759 | likely_benign | 0.1538 | benign | -0.045 | Destabilizing | 0.998 | D | 0.514 | neutral | None | None | None | None | N |
| R/L | 0.6048 | likely_pathogenic | 0.5355 | ambiguous | 0.573 | Stabilizing | 1.0 | D | 0.594 | neutral | N | 0.468050649 | None | None | N |
| R/M | 0.6149 | likely_pathogenic | 0.5519 | ambiguous | 0.035 | Stabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/N | 0.7544 | likely_pathogenic | 0.6649 | pathogenic | 0.086 | Stabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| R/P | 0.9545 | likely_pathogenic | 0.9333 | pathogenic | 0.44 | Stabilizing | 1.0 | D | 0.673 | neutral | D | 0.523655335 | None | None | N |
| R/Q | 0.1857 | likely_benign | 0.1533 | benign | 0.044 | Stabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| R/S | 0.7906 | likely_pathogenic | 0.6992 | pathogenic | -0.147 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | N | 0.453197959 | None | None | N |
| R/T | 0.6215 | likely_pathogenic | 0.5321 | ambiguous | 0.045 | Stabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| R/V | 0.7815 | likely_pathogenic | 0.7231 | pathogenic | 0.44 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| R/W | 0.4007 | ambiguous | 0.363 | ambiguous | -0.193 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| R/Y | 0.6312 | likely_pathogenic | 0.5747 | pathogenic | 0.213 | Stabilizing | 1.0 | D | 0.704 | 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.