Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27719 | 83380;83381;83382 | chr2:178562977;178562976;178562975 | chr2:179427704;179427703;179427702 |
| N2AB | 26078 | 78457;78458;78459 | chr2:178562977;178562976;178562975 | chr2:179427704;179427703;179427702 |
| N2A | 25151 | 75676;75677;75678 | chr2:178562977;178562976;178562975 | chr2:179427704;179427703;179427702 |
| N2B | 18654 | 56185;56186;56187 | chr2:178562977;178562976;178562975 | chr2:179427704;179427703;179427702 |
| Novex-1 | 18779 | 56560;56561;56562 | chr2:178562977;178562976;178562975 | chr2:179427704;179427703;179427702 |
| Novex-2 | 18846 | 56761;56762;56763 | chr2:178562977;178562976;178562975 | chr2:179427704;179427703;179427702 |
| 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/G | rs929458467  |
None | 0.025 | N | 0.385 | 0.206 | 0.319686207203 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 1.26695E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs1342825597 |
0.194 | 0.892 | N | 0.457 | 0.291 | 0.327952845175 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| R/S | rs1342825597 |
0.194 | 0.892 | N | 0.457 | 0.291 | 0.327952845175 | gnomAD-4.0.0 | 1.59155E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85855E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5677 | likely_pathogenic | 0.519 | ambiguous | -0.617 | Destabilizing | 0.845 | D | 0.471 | neutral | None | None | None | None | I |
| R/C | 0.3858 | ambiguous | 0.3616 | ambiguous | -0.433 | Destabilizing | 0.999 | D | 0.607 | neutral | None | None | None | None | I |
| R/D | 0.7364 | likely_pathogenic | 0.6879 | pathogenic | -0.064 | Destabilizing | 0.975 | D | 0.475 | neutral | None | None | None | None | I |
| R/E | 0.5258 | ambiguous | 0.4796 | ambiguous | 0.033 | Stabilizing | 0.957 | D | 0.466 | neutral | None | None | None | None | I |
| R/F | 0.8345 | likely_pathogenic | 0.7943 | pathogenic | -0.601 | Destabilizing | 0.996 | D | 0.566 | neutral | None | None | None | None | I |
| R/G | 0.4303 | ambiguous | 0.3712 | ambiguous | -0.903 | Destabilizing | 0.025 | N | 0.385 | neutral | N | 0.496516342 | None | None | I |
| R/H | 0.1614 | likely_benign | 0.1496 | benign | -1.275 | Destabilizing | 0.996 | D | 0.476 | neutral | None | None | None | None | I |
| R/I | 0.5973 | likely_pathogenic | 0.5345 | ambiguous | 0.141 | Stabilizing | 0.996 | D | 0.567 | neutral | None | None | None | None | I |
| R/K | 0.1226 | likely_benign | 0.1159 | benign | -0.624 | Destabilizing | 0.773 | D | 0.506 | neutral | N | 0.502695699 | None | None | I |
| R/L | 0.4927 | ambiguous | 0.4439 | ambiguous | 0.141 | Stabilizing | 0.987 | D | 0.443 | neutral | None | None | None | None | I |
| R/M | 0.5136 | ambiguous | 0.4565 | ambiguous | -0.057 | Destabilizing | 0.999 | D | 0.441 | neutral | N | 0.51597695 | None | None | I |
| R/N | 0.6693 | likely_pathogenic | 0.6121 | pathogenic | -0.021 | Destabilizing | 0.975 | D | 0.469 | neutral | None | None | None | None | I |
| R/P | 0.9128 | likely_pathogenic | 0.884 | pathogenic | -0.09 | Destabilizing | 0.996 | D | 0.495 | neutral | None | None | None | None | I |
| R/Q | 0.15 | likely_benign | 0.1399 | benign | -0.246 | Destabilizing | 0.996 | D | 0.529 | neutral | None | None | None | None | I |
| R/S | 0.6656 | likely_pathogenic | 0.6133 | pathogenic | -0.721 | Destabilizing | 0.892 | D | 0.457 | neutral | N | 0.491996892 | None | None | I |
| R/T | 0.4081 | ambiguous | 0.3438 | ambiguous | -0.457 | Destabilizing | 0.983 | D | 0.439 | neutral | N | 0.480640586 | None | None | I |
| R/V | 0.6557 | likely_pathogenic | 0.6043 | pathogenic | -0.09 | Destabilizing | 0.987 | D | 0.568 | neutral | None | None | None | None | I |
| R/W | 0.4891 | ambiguous | 0.4357 | ambiguous | -0.331 | Destabilizing | 0.999 | D | 0.628 | neutral | D | 0.527751329 | None | None | I |
| R/Y | 0.6697 | likely_pathogenic | 0.622 | pathogenic | -0.005 | Destabilizing | 0.996 | D | 0.495 | neutral | None | None | None | None | I |
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.