Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2351 | 7276;7277;7278 | chr2:178774213;178774212;178774211 | chr2:179638940;179638939;179638938 |
| N2AB | 2351 | 7276;7277;7278 | chr2:178774213;178774212;178774211 | chr2:179638940;179638939;179638938 |
| N2A | 2351 | 7276;7277;7278 | chr2:178774213;178774212;178774211 | chr2:179638940;179638939;179638938 |
| N2B | 2305 | 7138;7139;7140 | chr2:178774213;178774212;178774211 | chr2:179638940;179638939;179638938 |
| Novex-1 | 2305 | 7138;7139;7140 | chr2:178774213;178774212;178774211 | chr2:179638940;179638939;179638938 |
| Novex-2 | 2305 | 7138;7139;7140 | chr2:178774213;178774212;178774211 | chr2:179638940;179638939;179638938 |
| Novex-3 | 2351 | 7276;7277;7278 | chr2:178774213;178774212;178774211 | chr2:179638940;179638939;179638938 |
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/T | rs756899805  |
-1.766 | 0.801 | N | 0.549 | 0.41 | 0.412064437402 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| M/T | rs756899805 |
-1.766 | 0.801 | N | 0.549 | 0.41 | 0.412064437402 | gnomAD-4.0.0 | 1.5906E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.7508 | likely_pathogenic | 0.7645 | pathogenic | -2.491 | Highly Destabilizing | 0.525 | D | 0.506 | neutral | None | None | None | None | N |
| M/C | 0.8662 | likely_pathogenic | 0.8701 | pathogenic | -2.043 | Highly Destabilizing | 0.998 | D | 0.597 | neutral | None | None | None | None | N |
| M/D | 0.9822 | likely_pathogenic | 0.9819 | pathogenic | -1.912 | Destabilizing | 0.991 | D | 0.605 | neutral | None | None | None | None | N |
| M/E | 0.8642 | likely_pathogenic | 0.8714 | pathogenic | -1.816 | Destabilizing | 0.974 | D | 0.59 | neutral | None | None | None | None | N |
| M/F | 0.5454 | ambiguous | 0.5204 | ambiguous | -1.181 | Destabilizing | 0.974 | D | 0.619 | neutral | None | None | None | None | N |
| M/G | 0.8952 | likely_pathogenic | 0.8999 | pathogenic | -2.862 | Highly Destabilizing | 0.915 | D | 0.573 | neutral | None | None | None | None | N |
| M/H | 0.8856 | likely_pathogenic | 0.8847 | pathogenic | -2.085 | Highly Destabilizing | 0.998 | D | 0.595 | neutral | None | None | None | None | N |
| M/I | 0.3955 | ambiguous | 0.3899 | ambiguous | -1.47 | Destabilizing | 0.454 | N | 0.497 | neutral | N | 0.4084737 | None | None | N |
| M/K | 0.5751 | likely_pathogenic | 0.5983 | pathogenic | -1.529 | Destabilizing | 0.891 | D | 0.575 | neutral | N | 0.445633119 | None | None | N |
| M/L | 0.2004 | likely_benign | 0.2049 | benign | -1.47 | Destabilizing | 0.136 | N | 0.353 | neutral | N | 0.422755153 | None | None | N |
| M/N | 0.8456 | likely_pathogenic | 0.8431 | pathogenic | -1.5 | Destabilizing | 0.991 | D | 0.617 | neutral | None | None | None | None | N |
| M/P | 0.9272 | likely_pathogenic | 0.9277 | pathogenic | -1.79 | Destabilizing | 0.991 | D | 0.596 | neutral | None | None | None | None | N |
| M/Q | 0.539 | ambiguous | 0.5569 | ambiguous | -1.498 | Destabilizing | 0.991 | D | 0.627 | neutral | None | None | None | None | N |
| M/R | 0.5434 | ambiguous | 0.5695 | pathogenic | -1.124 | Destabilizing | 0.989 | D | 0.611 | neutral | N | 0.445633119 | None | None | N |
| M/S | 0.8237 | likely_pathogenic | 0.826 | pathogenic | -2.089 | Highly Destabilizing | 0.915 | D | 0.571 | neutral | None | None | None | None | N |
| M/T | 0.6524 | likely_pathogenic | 0.6685 | pathogenic | -1.893 | Destabilizing | 0.801 | D | 0.549 | neutral | N | 0.44491048 | None | None | N |
| M/V | 0.1602 | likely_benign | 0.1617 | benign | -1.79 | Destabilizing | 0.005 | N | 0.22 | neutral | N | 0.303842955 | None | None | N |
| M/W | 0.8242 | likely_pathogenic | 0.8163 | pathogenic | -1.247 | Destabilizing | 0.998 | D | 0.589 | neutral | None | None | None | None | N |
| M/Y | 0.7841 | likely_pathogenic | 0.7763 | pathogenic | -1.331 | Destabilizing | 0.991 | D | 0.614 | 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.