Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31948 | 96067;96068;96069 | chr2:178544387;178544386;178544385 | chr2:179409114;179409113;179409112 |
| N2AB | 30307 | 91144;91145;91146 | chr2:178544387;178544386;178544385 | chr2:179409114;179409113;179409112 |
| N2A | 29380 | 88363;88364;88365 | chr2:178544387;178544386;178544385 | chr2:179409114;179409113;179409112 |
| N2B | 22883 | 68872;68873;68874 | chr2:178544387;178544386;178544385 | chr2:179409114;179409113;179409112 |
| Novex-1 | 23008 | 69247;69248;69249 | chr2:178544387;178544386;178544385 | chr2:179409114;179409113;179409112 |
| Novex-2 | 23075 | 69448;69449;69450 | chr2:178544387;178544386;178544385 | chr2:179409114;179409113;179409112 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/L | None | None | 0.31 | N | 0.31 | 0.205 | 0.433047596574 | gnomAD-4.0.0 | 1.59135E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85863E-06 | 0 | 0 |
| M/T | rs377603482  |
-0.538 | 0.959 | N | 0.643 | 0.369 | None | gnomAD-2.1.1 | 3.93E-05 | None | None | None | None | N | None | 4.13257E-04 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs377603482 |
-0.538 | 0.959 | N | 0.643 | 0.369 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 2.17223E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs377603482 |
-0.538 | 0.959 | N | 0.643 | 0.369 | None | gnomAD-4.0.0 | 1.73523E-05 | None | None | None | None | N | None | 3.4713E-04 | 0 | None | 0 | 2.22906E-05 | None | 0 | 0 | 0 | 0 | 1.60118E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5569 | ambiguous | 0.6165 | pathogenic | -1.054 | Destabilizing | 0.863 | D | 0.591 | neutral | None | None | None | None | N |
| M/C | 0.6516 | likely_pathogenic | 0.6916 | pathogenic | -1.364 | Destabilizing | 0.997 | D | 0.711 | prob.delet. | None | None | None | None | N |
| M/D | 0.9847 | likely_pathogenic | 0.9871 | pathogenic | -1.525 | Destabilizing | 0.997 | D | 0.724 | prob.delet. | None | None | None | None | N |
| M/E | 0.8042 | likely_pathogenic | 0.8286 | pathogenic | -1.25 | Destabilizing | 0.99 | D | 0.666 | neutral | None | None | None | None | N |
| M/F | 0.3552 | ambiguous | 0.3487 | ambiguous | 0.057 | Stabilizing | 0.969 | D | 0.646 | neutral | None | None | None | None | N |
| M/G | 0.7886 | likely_pathogenic | 0.8357 | pathogenic | -1.542 | Destabilizing | 0.99 | D | 0.66 | neutral | None | None | None | None | N |
| M/H | 0.6953 | likely_pathogenic | 0.7272 | pathogenic | -1.688 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | N |
| M/I | 0.422 | ambiguous | 0.4424 | ambiguous | 0.359 | Stabilizing | 0.021 | N | 0.233 | neutral | N | 0.457699702 | None | None | N |
| M/K | 0.1969 | likely_benign | 0.2248 | benign | -0.52 | Destabilizing | 0.986 | D | 0.64 | neutral | N | 0.448984218 | None | None | N |
| M/L | 0.215 | likely_benign | 0.2414 | benign | 0.359 | Stabilizing | 0.31 | N | 0.31 | neutral | N | 0.488001179 | None | None | N |
| M/N | 0.8643 | likely_pathogenic | 0.8846 | pathogenic | -1.136 | Destabilizing | 0.997 | D | 0.699 | prob.neutral | None | None | None | None | N |
| M/P | 0.9971 | likely_pathogenic | 0.9975 | pathogenic | -0.096 | Destabilizing | 0.997 | D | 0.699 | prob.neutral | None | None | None | None | N |
| M/Q | 0.363 | ambiguous | 0.4043 | ambiguous | -0.659 | Destabilizing | 0.997 | D | 0.679 | prob.neutral | None | None | None | None | N |
| M/R | 0.2732 | likely_benign | 0.3123 | benign | -1.088 | Destabilizing | 0.996 | D | 0.686 | prob.neutral | N | 0.451389805 | None | None | N |
| M/S | 0.6821 | likely_pathogenic | 0.724 | pathogenic | -1.471 | Destabilizing | 0.99 | D | 0.641 | neutral | None | None | None | None | N |
| M/T | 0.4946 | ambiguous | 0.5356 | ambiguous | -1.06 | Destabilizing | 0.959 | D | 0.643 | neutral | N | 0.515862571 | None | None | N |
| M/V | 0.1568 | likely_benign | 0.1655 | benign | -0.096 | Destabilizing | 0.31 | N | 0.441 | neutral | N | 0.488001179 | None | None | N |
| M/W | 0.7442 | likely_pathogenic | 0.7421 | pathogenic | -0.418 | Destabilizing | 0.999 | D | 0.702 | prob.neutral | None | None | None | None | N |
| M/Y | 0.5568 | ambiguous | 0.5471 | ambiguous | -0.227 | Destabilizing | 0.997 | D | 0.698 | 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.