Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30274 | 91045;91046;91047 | chr2:178552080;178552079;178552078 | chr2:179416807;179416806;179416805 |
| N2AB | 28633 | 86122;86123;86124 | chr2:178552080;178552079;178552078 | chr2:179416807;179416806;179416805 |
| N2A | 27706 | 83341;83342;83343 | chr2:178552080;178552079;178552078 | chr2:179416807;179416806;179416805 |
| N2B | 21209 | 63850;63851;63852 | chr2:178552080;178552079;178552078 | chr2:179416807;179416806;179416805 |
| Novex-1 | 21334 | 64225;64226;64227 | chr2:178552080;178552079;178552078 | chr2:179416807;179416806;179416805 |
| Novex-2 | 21401 | 64426;64427;64428 | chr2:178552080;178552079;178552078 | chr2:179416807;179416806;179416805 |
| 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/I | rs898696376  |
-0.04 | 0.051 | N | 0.141 | 0.161 | 0.493628743246 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14837E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/I | rs898696376 |
-0.04 | 0.051 | N | 0.141 | 0.161 | 0.493628743246 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/I | rs898696376 |
-0.04 | 0.051 | N | 0.141 | 0.161 | 0.493628743246 | gnomAD-4.0.0 | 6.08991E-06 | None | None | None | None | N | None | 1.04877E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.6616 | likely_pathogenic | 0.58 | pathogenic | -0.929 | Destabilizing | 0.688 | D | 0.466 | neutral | None | None | None | None | N |
| M/C | 0.8793 | likely_pathogenic | 0.8576 | pathogenic | -0.825 | Destabilizing | 0.998 | D | 0.538 | neutral | None | None | None | None | N |
| M/D | 0.9467 | likely_pathogenic | 0.9166 | pathogenic | -0.002 | Destabilizing | 0.991 | D | 0.569 | neutral | None | None | None | None | N |
| M/E | 0.8111 | likely_pathogenic | 0.7285 | pathogenic | -0.036 | Destabilizing | 0.991 | D | 0.552 | neutral | None | None | None | None | N |
| M/F | 0.6224 | likely_pathogenic | 0.5789 | pathogenic | -0.375 | Destabilizing | 0.842 | D | 0.427 | neutral | None | None | None | None | N |
| M/G | 0.8854 | likely_pathogenic | 0.8461 | pathogenic | -1.154 | Destabilizing | 0.971 | D | 0.558 | neutral | None | None | None | None | N |
| M/H | 0.834 | likely_pathogenic | 0.7934 | pathogenic | -0.246 | Destabilizing | 0.998 | D | 0.533 | neutral | None | None | None | None | N |
| M/I | 0.456 | ambiguous | 0.3855 | ambiguous | -0.411 | Destabilizing | 0.051 | N | 0.141 | neutral | N | 0.416450512 | None | None | N |
| M/K | 0.652 | likely_pathogenic | 0.56 | ambiguous | 0.103 | Stabilizing | 0.891 | D | 0.531 | neutral | N | 0.416218439 | None | None | N |
| M/L | 0.1481 | likely_benign | 0.1659 | benign | -0.411 | Destabilizing | 0.002 | N | 0.134 | neutral | N | 0.457931775 | None | None | N |
| M/N | 0.7002 | likely_pathogenic | 0.6082 | pathogenic | 0.248 | Stabilizing | 0.991 | D | 0.561 | neutral | None | None | None | None | N |
| M/P | 0.6806 | likely_pathogenic | 0.6098 | pathogenic | -0.554 | Destabilizing | 0.991 | D | 0.561 | neutral | None | None | None | None | N |
| M/Q | 0.5814 | likely_pathogenic | 0.5054 | ambiguous | 0.072 | Stabilizing | 0.991 | D | 0.473 | neutral | None | None | None | None | N |
| M/R | 0.6556 | likely_pathogenic | 0.5922 | pathogenic | 0.631 | Stabilizing | 0.966 | D | 0.555 | neutral | N | 0.467049904 | None | None | N |
| M/S | 0.7624 | likely_pathogenic | 0.6947 | pathogenic | -0.28 | Destabilizing | 0.915 | D | 0.469 | neutral | None | None | None | None | N |
| M/T | 0.4834 | ambiguous | 0.4185 | ambiguous | -0.209 | Destabilizing | 0.891 | D | 0.475 | neutral | N | 0.379353561 | None | None | N |
| M/V | 0.1527 | likely_benign | 0.1358 | benign | -0.554 | Destabilizing | 0.267 | N | 0.2 | neutral | N | 0.411196621 | None | None | N |
| M/W | 0.8585 | likely_pathogenic | 0.8373 | pathogenic | -0.301 | Destabilizing | 0.998 | D | 0.53 | neutral | None | None | None | None | N |
| M/Y | 0.8032 | likely_pathogenic | 0.7694 | pathogenic | -0.212 | Destabilizing | 0.974 | D | 0.549 | 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.