Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31118 | 93577;93578;93579 | chr2:178548274;178548273;178548272 | chr2:179413001;179413000;179412999 |
| N2AB | 29477 | 88654;88655;88656 | chr2:178548274;178548273;178548272 | chr2:179413001;179413000;179412999 |
| N2A | 28550 | 85873;85874;85875 | chr2:178548274;178548273;178548272 | chr2:179413001;179413000;179412999 |
| N2B | 22053 | 66382;66383;66384 | chr2:178548274;178548273;178548272 | chr2:179413001;179413000;179412999 |
| Novex-1 | 22178 | 66757;66758;66759 | chr2:178548274;178548273;178548272 | chr2:179413001;179413000;179412999 |
| Novex-2 | 22245 | 66958;66959;66960 | chr2:178548274;178548273;178548272 | chr2:179413001;179413000;179412999 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs761397221  |
None | 0.117 | N | 0.517 | 0.242 | 0.202949470691 | gnomAD-4.0.0 | 2.73674E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69832E-06 | 0 | 1.65651E-05 |
| R/K | rs763830779 |
-0.139 | None | N | 0.124 | 0.07 | 0.110078149338 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/K | rs763830779 |
-0.139 | None | N | 0.124 | 0.07 | 0.110078149338 | gnomAD-4.0.0 | 1.59113E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 0 |
| R/S | rs2154147269 |
None | 0.027 | N | 0.518 | 0.11 | 0.0716867268079 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| R/S | rs2154147269 |
None | 0.027 | N | 0.518 | 0.11 | 0.0716867268079 | gnomAD-4.0.0 | 2.56178E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.6801E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3329 | likely_benign | 0.2937 | benign | -0.777 | Destabilizing | 0.035 | N | 0.495 | neutral | None | None | None | None | N |
| R/C | 0.2261 | likely_benign | 0.226 | benign | -0.689 | Destabilizing | 0.935 | D | 0.541 | neutral | None | None | None | None | N |
| R/D | 0.7584 | likely_pathogenic | 0.7257 | pathogenic | 0.003 | Stabilizing | 0.149 | N | 0.551 | neutral | None | None | None | None | N |
| R/E | 0.4031 | ambiguous | 0.3433 | ambiguous | 0.165 | Stabilizing | 0.035 | N | 0.5 | neutral | None | None | None | None | N |
| R/F | 0.6603 | likely_pathogenic | 0.5926 | pathogenic | -0.341 | Destabilizing | 0.791 | D | 0.55 | neutral | None | None | None | None | N |
| R/G | 0.2051 | likely_benign | 0.1672 | benign | -1.137 | Destabilizing | 0.117 | N | 0.517 | neutral | N | 0.389669343 | None | None | N |
| R/H | 0.1694 | likely_benign | 0.1671 | benign | -1.377 | Destabilizing | 0.555 | D | 0.567 | neutral | None | None | None | None | N |
| R/I | 0.3418 | ambiguous | 0.3026 | benign | 0.207 | Stabilizing | 0.555 | D | 0.556 | neutral | None | None | None | None | N |
| R/K | 0.0681 | likely_benign | 0.0601 | benign | -0.753 | Destabilizing | None | N | 0.124 | neutral | N | 0.426648863 | None | None | N |
| R/L | 0.2665 | likely_benign | 0.227 | benign | 0.207 | Stabilizing | 0.149 | N | 0.517 | neutral | None | None | None | None | N |
| R/M | 0.295 | likely_benign | 0.2504 | benign | -0.242 | Destabilizing | 0.741 | D | 0.579 | neutral | N | 0.472749299 | None | None | N |
| R/N | 0.6022 | likely_pathogenic | 0.5332 | ambiguous | -0.326 | Destabilizing | 0.149 | N | 0.505 | neutral | None | None | None | None | N |
| R/P | 0.6861 | likely_pathogenic | 0.6768 | pathogenic | -0.1 | Destabilizing | 0.262 | N | 0.565 | neutral | None | None | None | None | N |
| R/Q | 0.1027 | likely_benign | 0.094 | benign | -0.366 | Destabilizing | 0.081 | N | 0.511 | neutral | None | None | None | None | N |
| R/S | 0.4556 | ambiguous | 0.397 | ambiguous | -1.086 | Destabilizing | 0.027 | N | 0.518 | neutral | N | 0.415103718 | None | None | N |
| R/T | 0.2641 | likely_benign | 0.225 | benign | -0.721 | Destabilizing | 0.117 | N | 0.542 | neutral | N | 0.427590226 | None | None | N |
| R/V | 0.3591 | ambiguous | 0.3187 | benign | -0.1 | Destabilizing | 0.149 | N | 0.563 | neutral | None | None | None | None | N |
| R/W | 0.3389 | likely_benign | 0.2989 | benign | 0.036 | Stabilizing | 0.915 | D | 0.579 | neutral | N | 0.469877982 | None | None | N |
| R/Y | 0.5418 | ambiguous | 0.4955 | ambiguous | 0.288 | Stabilizing | 0.555 | D | 0.559 | 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.