Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13931 | 42016;42017;42018 | chr2:178635533;178635532;178635531 | chr2:179500260;179500259;179500258 |
| N2AB | 12290 | 37093;37094;37095 | chr2:178635533;178635532;178635531 | chr2:179500260;179500259;179500258 |
| N2A | 11363 | 34312;34313;34314 | chr2:178635533;178635532;178635531 | chr2:179500260;179500259;179500258 |
| N2B | 4866 | 14821;14822;14823 | chr2:178635533;178635532;178635531 | chr2:179500260;179500259;179500258 |
| Novex-1 | 4991 | 15196;15197;15198 | chr2:178635533;178635532;178635531 | chr2:179500260;179500259;179500258 |
| Novex-2 | 5058 | 15397;15398;15399 | chr2:178635533;178635532;178635531 | chr2:179500260;179500259;179500258 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | None | None | 0.257 | N | 0.487 | 0.085 | 0.0482279557977 | gnomAD-4.0.0 | 1.38395E-06 | None | None | None | None | N | None | 3.0021E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.06918E-07 | 0 | 0 |
| Y/H | rs1162801145  |
-1.606 | None | N | 0.171 | 0.057 | 0.0762999501168 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| Y/H | rs1162801145 |
-1.606 | None | N | 0.171 | 0.057 | 0.0762999501168 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Y/H | rs1162801145 |
-1.606 | None | N | 0.171 | 0.057 | 0.0762999501168 | gnomAD-4.0.0 | 6.57488E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47111E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.511 | ambiguous | 0.6153 | pathogenic | -2.933 | Highly Destabilizing | 0.004 | N | 0.365 | neutral | None | None | None | None | N |
| Y/C | 0.18 | likely_benign | 0.236 | benign | -1.299 | Destabilizing | 0.257 | N | 0.487 | neutral | N | 0.445407988 | None | None | N |
| Y/D | 0.6256 | likely_pathogenic | 0.6964 | pathogenic | -2.238 | Highly Destabilizing | 0.003 | N | 0.403 | neutral | N | 0.444389228 | None | None | N |
| Y/E | 0.6627 | likely_pathogenic | 0.7637 | pathogenic | -2.12 | Highly Destabilizing | None | N | 0.289 | neutral | None | None | None | None | N |
| Y/F | 0.0623 | likely_benign | 0.0745 | benign | -1.228 | Destabilizing | None | N | 0.083 | neutral | N | 0.37658292 | None | None | N |
| Y/G | 0.6805 | likely_pathogenic | 0.7494 | pathogenic | -3.287 | Highly Destabilizing | 0.009 | N | 0.415 | neutral | None | None | None | None | N |
| Y/H | 0.1274 | likely_benign | 0.1677 | benign | -1.678 | Destabilizing | None | N | 0.171 | neutral | N | 0.416479225 | None | None | N |
| Y/I | 0.2812 | likely_benign | 0.3257 | benign | -1.802 | Destabilizing | None | N | 0.203 | neutral | None | None | None | None | N |
| Y/K | 0.6761 | likely_pathogenic | 0.7315 | pathogenic | -1.701 | Destabilizing | None | N | 0.31 | neutral | None | None | None | None | N |
| Y/L | 0.3738 | ambiguous | 0.4475 | ambiguous | -1.802 | Destabilizing | 0.001 | N | 0.285 | neutral | None | None | None | None | N |
| Y/M | 0.4874 | ambiguous | 0.5747 | pathogenic | -1.299 | Destabilizing | 0.069 | N | 0.379 | neutral | None | None | None | None | N |
| Y/N | 0.2933 | likely_benign | 0.3676 | ambiguous | -2.085 | Highly Destabilizing | 0.008 | N | 0.477 | neutral | N | 0.443227221 | None | None | N |
| Y/P | 0.986 | likely_pathogenic | 0.9893 | pathogenic | -2.183 | Highly Destabilizing | 0.041 | N | 0.549 | neutral | None | None | None | None | N |
| Y/Q | 0.4322 | ambiguous | 0.5411 | ambiguous | -2.018 | Highly Destabilizing | 0.021 | N | 0.497 | neutral | None | None | None | None | N |
| Y/R | 0.5099 | ambiguous | 0.5553 | ambiguous | -1.198 | Destabilizing | 0.01 | N | 0.517 | neutral | None | None | None | None | N |
| Y/S | 0.2168 | likely_benign | 0.302 | benign | -2.549 | Highly Destabilizing | 0.003 | N | 0.355 | neutral | N | 0.411373222 | None | None | N |
| Y/T | 0.3155 | likely_benign | 0.4266 | ambiguous | -2.336 | Highly Destabilizing | None | N | 0.244 | neutral | None | None | None | None | N |
| Y/V | 0.2533 | likely_benign | 0.3176 | benign | -2.183 | Highly Destabilizing | 0.001 | N | 0.323 | neutral | None | None | None | None | N |
| Y/W | 0.377 | ambiguous | 0.4032 | ambiguous | -0.707 | Destabilizing | 0.131 | N | 0.467 | 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.