Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20886 | 62881;62882;62883 | chr2:178589069;178589068;178589067 | chr2:179453796;179453795;179453794 |
| N2AB | 19245 | 57958;57959;57960 | chr2:178589069;178589068;178589067 | chr2:179453796;179453795;179453794 |
| N2A | 18318 | 55177;55178;55179 | chr2:178589069;178589068;178589067 | chr2:179453796;179453795;179453794 |
| N2B | 11821 | 35686;35687;35688 | chr2:178589069;178589068;178589067 | chr2:179453796;179453795;179453794 |
| Novex-1 | 11946 | 36061;36062;36063 | chr2:178589069;178589068;178589067 | chr2:179453796;179453795;179453794 |
| Novex-2 | 12013 | 36262;36263;36264 | chr2:178589069;178589068;178589067 | chr2:179453796;179453795;179453794 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs1381546881  |
-0.618 | 0.117 | N | 0.206 | 0.047 | 0.151104730317 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs1381546881 |
-0.618 | 0.117 | N | 0.206 | 0.047 | 0.151104730317 | 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 |
| D/E | rs1381546881 |
-0.618 | 0.117 | N | 0.206 | 0.047 | 0.151104730317 | gnomAD-4.0.0 | 6.57678E-06 | None | None | None | None | N | None | 2.41348E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/G | None | None | 0.977 | N | 0.689 | 0.369 | 0.351614576976 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/N | rs1445324473 |
-1.096 | 0.993 | N | 0.671 | 0.319 | 0.348983352498 | gnomAD-2.1.1 | 8.16E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| D/N | rs1445324473 |
-1.096 | 0.993 | N | 0.671 | 0.319 | 0.348983352498 | gnomAD-4.0.0 | 4.80654E-06 | None | None | None | None | N | None | 0 | 2.28906E-05 | None | 0 | 0 | None | 0 | 0 | 5.71925E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.264 | likely_benign | 0.2525 | benign | -0.407 | Destabilizing | 0.977 | D | 0.703 | prob.neutral | N | 0.466244614 | None | None | N |
| D/C | 0.7619 | likely_pathogenic | 0.7687 | pathogenic | -0.365 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| D/E | 0.152 | likely_benign | 0.1549 | benign | -0.913 | Destabilizing | 0.117 | N | 0.206 | neutral | N | 0.426376717 | None | None | N |
| D/F | 0.6816 | likely_pathogenic | 0.6509 | pathogenic | -0.073 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| D/G | 0.3485 | ambiguous | 0.3059 | benign | -0.786 | Destabilizing | 0.977 | D | 0.689 | prob.neutral | N | 0.509592747 | None | None | N |
| D/H | 0.4719 | ambiguous | 0.4521 | ambiguous | -0.583 | Destabilizing | 0.999 | D | 0.802 | deleterious | N | 0.485144627 | None | None | N |
| D/I | 0.4127 | ambiguous | 0.4188 | ambiguous | 0.602 | Stabilizing | 0.998 | D | 0.854 | deleterious | None | None | None | None | N |
| D/K | 0.5713 | likely_pathogenic | 0.566 | pathogenic | -0.919 | Destabilizing | 0.99 | D | 0.751 | deleterious | None | None | None | None | N |
| D/L | 0.3926 | ambiguous | 0.387 | ambiguous | 0.602 | Stabilizing | 0.995 | D | 0.845 | deleterious | None | None | None | None | N |
| D/M | 0.5951 | likely_pathogenic | 0.5968 | pathogenic | 1.047 | Stabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| D/N | 0.1606 | likely_benign | 0.1476 | benign | -1.247 | Destabilizing | 0.993 | D | 0.671 | neutral | N | 0.474344022 | None | None | N |
| D/P | 0.9662 | likely_pathogenic | 0.9657 | pathogenic | 0.292 | Stabilizing | 0.998 | D | 0.806 | deleterious | None | None | None | None | N |
| D/Q | 0.4241 | ambiguous | 0.4337 | ambiguous | -1.032 | Destabilizing | 0.99 | D | 0.72 | prob.delet. | None | None | None | None | N |
| D/R | 0.6655 | likely_pathogenic | 0.6547 | pathogenic | -0.765 | Destabilizing | 0.995 | D | 0.824 | deleterious | None | None | None | None | N |
| D/S | 0.1907 | likely_benign | 0.1833 | benign | -1.533 | Destabilizing | 0.983 | D | 0.605 | neutral | None | None | None | None | N |
| D/T | 0.3337 | likely_benign | 0.3417 | ambiguous | -1.23 | Destabilizing | 0.995 | D | 0.737 | prob.delet. | None | None | None | None | N |
| D/V | 0.2659 | likely_benign | 0.2762 | benign | 0.292 | Stabilizing | 0.997 | D | 0.844 | deleterious | N | 0.509419388 | None | None | N |
| D/W | 0.9212 | likely_pathogenic | 0.9164 | pathogenic | -0.062 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| D/Y | 0.3264 | likely_benign | 0.3063 | benign | 0.079 | Stabilizing | 1.0 | D | 0.853 | deleterious | N | 0.521887253 | 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.