Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21972 | 66139;66140;66141 | chr2:178582542;178582541;178582540 | chr2:179447269;179447268;179447267 |
| N2AB | 20331 | 61216;61217;61218 | chr2:178582542;178582541;178582540 | chr2:179447269;179447268;179447267 |
| N2A | 19404 | 58435;58436;58437 | chr2:178582542;178582541;178582540 | chr2:179447269;179447268;179447267 |
| N2B | 12907 | 38944;38945;38946 | chr2:178582542;178582541;178582540 | chr2:179447269;179447268;179447267 |
| Novex-1 | 13032 | 39319;39320;39321 | chr2:178582542;178582541;178582540 | chr2:179447269;179447268;179447267 |
| Novex-2 | 13099 | 39520;39521;39522 | chr2:178582542;178582541;178582540 | chr2:179447269;179447268;179447267 |
| 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 | rs755916258  |
-1.516 | 0.999 | N | 0.596 | 0.375 | None | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| R/C | rs755916258 |
-1.516 | 0.999 | N | 0.596 | 0.375 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/C | rs755916258 |
-1.516 | 0.999 | N | 0.596 | 0.375 | None | gnomAD-4.0.0 | 1.92258E-05 | None | None | None | None | N | None | 4.00994E-05 | 0 | None | 0 | 0 | None | 0 | 1.65017E-04 | 2.20506E-05 | 0 | 1.60272E-05 |
| R/H | rs200217934 |
-2.16 | 0.081 | N | 0.381 | 0.13 | None | gnomAD-2.1.1 | 7.53E-05 | None | None | None | None | N | None | 4.14E-05 | 5.67E-05 | None | 0 | 0 | None | 6.55E-05 | None | 4.01E-05 | 1.17782E-04 | 0 |
| R/H | rs200217934 |
-2.16 | 0.081 | N | 0.381 | 0.13 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.02999E-04 | 0 | 0 |
| R/H | rs200217934 |
-2.16 | 0.081 | N | 0.381 | 0.13 | None | gnomAD-4.0.0 | 8.80622E-05 | None | None | None | None | N | None | 1.33708E-05 | 5.00701E-05 | None | 0 | 0 | None | 0 | 0 | 1.11096E-04 | 4.3956E-05 | 4.80785E-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 | 0.8169 | likely_pathogenic | 0.7113 | pathogenic | -1.402 | Destabilizing | 0.543 | D | 0.465 | neutral | None | None | None | None | N |
| R/C | 0.3529 | ambiguous | 0.258 | benign | -1.475 | Destabilizing | 0.999 | D | 0.596 | neutral | N | 0.477192327 | None | None | N |
| R/D | 0.9529 | likely_pathogenic | 0.9278 | pathogenic | -0.679 | Destabilizing | 0.91 | D | 0.609 | neutral | None | None | None | None | N |
| R/E | 0.7521 | likely_pathogenic | 0.6629 | pathogenic | -0.512 | Destabilizing | 0.742 | D | 0.506 | neutral | None | None | None | None | N |
| R/F | 0.8313 | likely_pathogenic | 0.7488 | pathogenic | -1.006 | Destabilizing | 0.91 | D | 0.599 | neutral | None | None | None | None | N |
| R/G | 0.6935 | likely_pathogenic | 0.5693 | pathogenic | -1.75 | Destabilizing | 0.017 | N | 0.413 | neutral | N | 0.503357421 | None | None | N |
| R/H | 0.1392 | likely_benign | 0.1151 | benign | -1.81 | Destabilizing | 0.081 | N | 0.381 | neutral | N | 0.47926984 | None | None | N |
| R/I | 0.7007 | likely_pathogenic | 0.5799 | pathogenic | -0.435 | Destabilizing | 0.02 | N | 0.437 | neutral | None | None | None | None | N |
| R/K | 0.1593 | likely_benign | 0.1321 | benign | -1.432 | Destabilizing | 0.742 | D | 0.505 | neutral | None | None | None | None | N |
| R/L | 0.681 | likely_pathogenic | 0.5644 | pathogenic | -0.435 | Destabilizing | 0.487 | N | 0.519 | neutral | N | 0.475901462 | None | None | N |
| R/M | 0.6131 | likely_pathogenic | 0.4898 | ambiguous | -0.762 | Destabilizing | 0.91 | D | 0.573 | neutral | None | None | None | None | N |
| R/N | 0.8708 | likely_pathogenic | 0.806 | pathogenic | -1.08 | Destabilizing | 0.742 | D | 0.543 | neutral | None | None | None | None | N |
| R/P | 0.996 | likely_pathogenic | 0.993 | pathogenic | -0.74 | Destabilizing | 0.992 | D | 0.607 | neutral | N | 0.487675841 | None | None | N |
| R/Q | 0.1912 | likely_benign | 0.1549 | benign | -1.121 | Destabilizing | 0.91 | D | 0.566 | neutral | None | None | None | None | N |
| R/S | 0.804 | likely_pathogenic | 0.7123 | pathogenic | -1.906 | Destabilizing | 0.846 | D | 0.499 | neutral | N | 0.370747147 | None | None | N |
| R/T | 0.5719 | likely_pathogenic | 0.4432 | ambiguous | -1.537 | Destabilizing | 0.742 | D | 0.559 | neutral | None | None | None | None | N |
| R/V | 0.7492 | likely_pathogenic | 0.6401 | pathogenic | -0.74 | Destabilizing | 0.331 | N | 0.563 | neutral | None | None | None | None | N |
| R/W | 0.4722 | ambiguous | 0.4068 | ambiguous | -0.573 | Destabilizing | 0.996 | D | 0.618 | neutral | None | None | None | None | N |
| R/Y | 0.688 | likely_pathogenic | 0.5908 | pathogenic | -0.317 | Destabilizing | 0.91 | D | 0.605 | 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.