Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1882 | 5869;5870;5871 | chr2:178776220;178776219;178776218 | chr2:179640947;179640946;179640945 |
| N2AB | 1882 | 5869;5870;5871 | chr2:178776220;178776219;178776218 | chr2:179640947;179640946;179640945 |
| N2A | 1882 | 5869;5870;5871 | chr2:178776220;178776219;178776218 | chr2:179640947;179640946;179640945 |
| N2B | 1836 | 5731;5732;5733 | chr2:178776220;178776219;178776218 | chr2:179640947;179640946;179640945 |
| Novex-1 | 1836 | 5731;5732;5733 | chr2:178776220;178776219;178776218 | chr2:179640947;179640946;179640945 |
| Novex-2 | 1836 | 5731;5732;5733 | chr2:178776220;178776219;178776218 | chr2:179640947;179640946;179640945 |
| Novex-3 | 1882 | 5869;5870;5871 | chr2:178776220;178776219;178776218 | chr2:179640947;179640946;179640945 |
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 | rs397517658  |
-0.199 | 1.0 | D | 0.649 | 0.597 | 0.731740448394 | gnomAD-2.1.1 | 2.12E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.88E-05 | 0 |
| R/C | rs397517658 |
-0.199 | 1.0 | D | 0.649 | 0.597 | 0.731740448394 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| R/C | rs397517658 |
-0.199 | 1.0 | D | 0.649 | 0.597 | 0.731740448394 | gnomAD-4.0.0 | 2.72615E-05 | None | None | None | None | N | None | 5.34017E-05 | 0 | None | 0 | 0 | None | 0 | 4.93097E-04 | 2.7966E-05 | 3.29345E-05 | 1.60046E-05 |
| R/H | rs374605213 |
-0.742 | 0.783 | N | 0.336 | 0.342 | None | gnomAD-2.1.1 | 6.37E-05 | None | None | None | None | N | None | 0 | 1.69367E-04 | None | 0 | 0 | None | 1.63313E-04 | None | 3.98E-05 | 4.66E-05 | 0 |
| R/H | rs374605213 |
-0.742 | 0.783 | N | 0.336 | 0.342 | None | gnomAD-3.1.2 | 1.77424E-04 | None | None | None | None | N | None | 4.83E-05 | 8.51008E-04 | 0 | 2.88351E-04 | 1.92382E-04 | None | 9.43E-05 | 0 | 1.32287E-04 | 0 | 0 |
| R/H | rs374605213 |
-0.742 | 0.783 | N | 0.336 | 0.342 | None | gnomAD-4.0.0 | 5.20447E-05 | None | None | None | None | N | None | 2.66951E-05 | 3.16667E-04 | None | 6.7563E-05 | 2.22737E-05 | None | 3.12402E-05 | 0 | 3.30511E-05 | 1.31744E-04 | 1.12029E-04 |
| R/S | None | None | 0.998 | N | 0.532 | 0.561 | 0.497280371566 | gnomAD-4.0.0 | 6.84077E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99306E-07 | 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 | 0.9832 | likely_pathogenic | 0.9596 | pathogenic | 0.058 | Stabilizing | 0.996 | D | 0.576 | neutral | None | None | None | None | N |
| R/C | 0.9165 | likely_pathogenic | 0.8087 | pathogenic | -0.34 | Destabilizing | 1.0 | D | 0.649 | neutral | D | 0.554732472 | None | None | N |
| R/D | 0.994 | likely_pathogenic | 0.9866 | pathogenic | -0.4 | Destabilizing | 0.999 | D | 0.562 | neutral | None | None | None | None | N |
| R/E | 0.9708 | likely_pathogenic | 0.9334 | pathogenic | -0.358 | Destabilizing | 0.992 | D | 0.548 | neutral | None | None | None | None | N |
| R/F | 0.9882 | likely_pathogenic | 0.9749 | pathogenic | -0.293 | Destabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| R/G | 0.9447 | likely_pathogenic | 0.8818 | pathogenic | -0.071 | Destabilizing | 0.998 | D | 0.499 | neutral | N | 0.507225092 | None | None | N |
| R/H | 0.7433 | likely_pathogenic | 0.5386 | ambiguous | -0.618 | Destabilizing | 0.783 | D | 0.336 | neutral | N | 0.50921065 | None | None | N |
| R/I | 0.9795 | likely_pathogenic | 0.9462 | pathogenic | 0.351 | Stabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| R/K | 0.5451 | ambiguous | 0.3859 | ambiguous | -0.234 | Destabilizing | 0.99 | D | 0.526 | neutral | None | None | None | None | N |
| R/L | 0.9298 | likely_pathogenic | 0.8615 | pathogenic | 0.351 | Stabilizing | 0.999 | D | 0.501 | neutral | N | 0.50478194 | None | None | N |
| R/M | 0.9833 | likely_pathogenic | 0.9535 | pathogenic | -0.158 | Destabilizing | 1.0 | D | 0.564 | neutral | None | None | None | None | N |
| R/N | 0.9907 | likely_pathogenic | 0.9771 | pathogenic | -0.248 | Destabilizing | 0.992 | D | 0.528 | neutral | None | None | None | None | N |
| R/P | 0.9784 | likely_pathogenic | 0.9565 | pathogenic | 0.271 | Stabilizing | 1.0 | D | 0.608 | neutral | N | 0.49419543 | None | None | N |
| R/Q | 0.7175 | likely_pathogenic | 0.4987 | ambiguous | -0.231 | Destabilizing | 0.999 | D | 0.539 | neutral | None | None | None | None | N |
| R/S | 0.9831 | likely_pathogenic | 0.9609 | pathogenic | -0.347 | Destabilizing | 0.998 | D | 0.532 | neutral | N | 0.48091238 | None | None | N |
| R/T | 0.9782 | likely_pathogenic | 0.9423 | pathogenic | -0.202 | Destabilizing | 1.0 | D | 0.499 | neutral | None | None | None | None | N |
| R/V | 0.9778 | likely_pathogenic | 0.9488 | pathogenic | 0.271 | Stabilizing | 1.0 | D | 0.658 | neutral | None | None | None | None | N |
| R/W | 0.8936 | likely_pathogenic | 0.7727 | pathogenic | -0.529 | Destabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| R/Y | 0.9702 | likely_pathogenic | 0.9344 | pathogenic | -0.119 | Destabilizing | 0.998 | D | 0.612 | 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.