Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28322 | 85189;85190;85191 | chr2:178561168;178561167;178561166 | chr2:179425895;179425894;179425893 |
| N2AB | 26681 | 80266;80267;80268 | chr2:178561168;178561167;178561166 | chr2:179425895;179425894;179425893 |
| N2A | 25754 | 77485;77486;77487 | chr2:178561168;178561167;178561166 | chr2:179425895;179425894;179425893 |
| N2B | 19257 | 57994;57995;57996 | chr2:178561168;178561167;178561166 | chr2:179425895;179425894;179425893 |
| Novex-1 | 19382 | 58369;58370;58371 | chr2:178561168;178561167;178561166 | chr2:179425895;179425894;179425893 |
| Novex-2 | 19449 | 58570;58571;58572 | chr2:178561168;178561167;178561166 | chr2:179425895;179425894;179425893 |
| 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/C | rs774978209  |
-1.072 | 0.999 | N | 0.521 | 0.354 | 0.51847606553 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 1.29216E-04 | 0 | None | 0 | 0 | None | 1.3071E-04 | None | 0 | 0 | 0 |
| R/C | rs774978209 |
-1.072 | 0.999 | N | 0.521 | 0.354 | 0.51847606553 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 1.20685E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs774978209 |
-1.072 | 0.999 | N | 0.521 | 0.354 | 0.51847606553 | gnomAD-4.0.0 | 2.72708E-05 | None | None | None | None | N | None | 8.01068E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54281E-05 | 7.68589E-05 | 1.60118E-05 |
| R/H | rs373532064 |
-1.666 | 0.081 | N | 0.178 | 0.184 | None | gnomAD-2.1.1 | 5.36E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 5.14E-05 | None | 0 | None | 0 | 9.4E-05 | 0 |
| R/H | rs373532064 |
-1.666 | 0.081 | N | 0.178 | 0.184 | None | gnomAD-3.1.2 | 8.54E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47029E-04 | 0 | 0 |
| R/H | rs373532064 |
-1.666 | 0.081 | N | 0.178 | 0.184 | None | gnomAD-4.0.0 | 1.13414E-04 | None | None | None | None | N | None | 4.00491E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4155E-04 | 0 | 2.0814E-04 |
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 | 0.3592 | ambiguous | 0.3485 | ambiguous | -0.888 | Destabilizing | 0.373 | N | 0.423 | neutral | None | None | None | None | N |
| R/C | 0.1608 | likely_benign | 0.1652 | benign | -0.924 | Destabilizing | 0.999 | D | 0.521 | neutral | N | 0.47188899 | None | None | N |
| R/D | 0.6711 | likely_pathogenic | 0.6688 | pathogenic | -0.022 | Destabilizing | 0.742 | D | 0.477 | neutral | None | None | None | None | N |
| R/E | 0.305 | likely_benign | 0.3082 | benign | 0.161 | Stabilizing | 0.373 | N | 0.428 | neutral | None | None | None | None | N |
| R/F | 0.5778 | likely_pathogenic | 0.5761 | pathogenic | -0.332 | Destabilizing | 0.953 | D | 0.513 | neutral | None | None | None | None | N |
| R/G | 0.3166 | likely_benign | 0.2989 | benign | -1.247 | Destabilizing | 0.846 | D | 0.445 | neutral | N | 0.508283238 | None | None | N |
| R/H | 0.113 | likely_benign | 0.1137 | benign | -1.281 | Destabilizing | 0.081 | N | 0.178 | neutral | N | 0.482231338 | None | None | N |
| R/I | 0.2488 | likely_benign | 0.247 | benign | 0.105 | Stabilizing | 0.91 | D | 0.519 | neutral | None | None | None | None | N |
| R/K | 0.1065 | likely_benign | 0.1085 | benign | -0.722 | Destabilizing | 0.373 | N | 0.443 | neutral | None | None | None | None | N |
| R/L | 0.212 | likely_benign | 0.215 | benign | 0.105 | Stabilizing | 0.734 | D | 0.445 | neutral | N | 0.49419922 | None | None | N |
| R/M | 0.2451 | likely_benign | 0.249 | benign | -0.482 | Destabilizing | 0.984 | D | 0.475 | neutral | None | None | None | None | N |
| R/N | 0.5064 | ambiguous | 0.4958 | ambiguous | -0.503 | Destabilizing | 0.742 | D | 0.434 | neutral | None | None | None | None | N |
| R/P | 0.5484 | ambiguous | 0.495 | ambiguous | -0.207 | Destabilizing | 0.975 | D | 0.476 | neutral | N | 0.493121784 | None | None | N |
| R/Q | 0.0945 | likely_benign | 0.0933 | benign | -0.483 | Destabilizing | 0.101 | N | 0.113 | neutral | None | None | None | None | N |
| R/S | 0.4206 | ambiguous | 0.4072 | ambiguous | -1.287 | Destabilizing | 0.734 | D | 0.418 | neutral | N | 0.436844427 | None | None | N |
| R/T | 0.1956 | likely_benign | 0.1985 | benign | -0.896 | Destabilizing | 0.009 | N | 0.213 | neutral | None | None | None | None | N |
| R/V | 0.3085 | likely_benign | 0.3081 | benign | -0.207 | Destabilizing | 0.59 | D | 0.489 | neutral | None | None | None | None | N |
| R/W | 0.2342 | likely_benign | 0.2391 | benign | 0.07 | Stabilizing | 0.996 | D | 0.537 | neutral | None | None | None | None | N |
| R/Y | 0.379 | ambiguous | 0.3742 | ambiguous | 0.295 | Stabilizing | 0.91 | D | 0.503 | 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.