Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22989 | 69190;69191;69192 | chr2:178577370;178577369;178577368 | chr2:179442097;179442096;179442095 |
| N2AB | 21348 | 64267;64268;64269 | chr2:178577370;178577369;178577368 | chr2:179442097;179442096;179442095 |
| N2A | 20421 | 61486;61487;61488 | chr2:178577370;178577369;178577368 | chr2:179442097;179442096;179442095 |
| N2B | 13924 | 41995;41996;41997 | chr2:178577370;178577369;178577368 | chr2:179442097;179442096;179442095 |
| Novex-1 | 14049 | 42370;42371;42372 | chr2:178577370;178577369;178577368 | chr2:179442097;179442096;179442095 |
| Novex-2 | 14116 | 42571;42572;42573 | chr2:178577370;178577369;178577368 | chr2:179442097;179442096;179442095 |
| 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/K | None | None | 0.002 | N | 0.233 | 0.134 | 0.197625483188 | gnomAD-4.0.0 | 6.84373E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99599E-07 | 0 | 0 |
| R/S | rs1295839847  |
None | 0.801 | N | 0.516 | 0.257 | 0.266843984389 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| R/S | rs1295839847 |
None | 0.801 | N | 0.516 | 0.257 | 0.266843984389 | gnomAD-4.0.0 | 1.59214E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77932E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | None | None | 0.801 | N | 0.518 | 0.263 | 0.529763130185 | gnomAD-4.0.0 | 1.36875E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7992E-06 | 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 | 0.2737 | likely_benign | 0.2415 | benign | 0.126 | Stabilizing | 0.688 | D | 0.487 | neutral | None | None | None | None | N |
| R/C | 0.1391 | likely_benign | 0.1164 | benign | -0.159 | Destabilizing | 0.998 | D | 0.475 | neutral | None | None | None | None | N |
| R/D | 0.5642 | likely_pathogenic | 0.4769 | ambiguous | -0.3 | Destabilizing | 0.842 | D | 0.468 | neutral | None | None | None | None | N |
| R/E | 0.3029 | likely_benign | 0.2465 | benign | -0.257 | Destabilizing | 0.525 | D | 0.491 | neutral | None | None | None | None | N |
| R/F | 0.3546 | ambiguous | 0.3025 | benign | -0.186 | Destabilizing | 0.991 | D | 0.465 | neutral | None | None | None | None | N |
| R/G | 0.2091 | likely_benign | 0.1771 | benign | -0.015 | Destabilizing | 0.801 | D | 0.502 | neutral | N | 0.463834319 | None | None | N |
| R/H | 0.0901 | likely_benign | 0.0804 | benign | -0.573 | Destabilizing | 0.991 | D | 0.479 | neutral | None | None | None | None | N |
| R/I | 0.148 | likely_benign | 0.1317 | benign | 0.451 | Stabilizing | 0.966 | D | 0.476 | neutral | N | 0.444344481 | None | None | N |
| R/K | 0.0761 | likely_benign | 0.0702 | benign | -0.073 | Destabilizing | 0.002 | N | 0.233 | neutral | N | 0.376559264 | None | None | N |
| R/L | 0.1565 | likely_benign | 0.1403 | benign | 0.451 | Stabilizing | 0.842 | D | 0.502 | neutral | None | None | None | None | N |
| R/M | 0.1866 | likely_benign | 0.1612 | benign | -0.045 | Destabilizing | 0.991 | D | 0.46 | neutral | None | None | None | None | N |
| R/N | 0.4321 | ambiguous | 0.3656 | ambiguous | 0.006 | Stabilizing | 0.842 | D | 0.496 | neutral | None | None | None | None | N |
| R/P | 0.3439 | ambiguous | 0.2919 | benign | 0.361 | Stabilizing | 0.974 | D | 0.461 | neutral | None | None | None | None | N |
| R/Q | 0.0929 | likely_benign | 0.0831 | benign | -0.011 | Destabilizing | 0.842 | D | 0.527 | neutral | None | None | None | None | N |
| R/S | 0.3293 | likely_benign | 0.2806 | benign | -0.124 | Destabilizing | 0.801 | D | 0.516 | neutral | N | 0.42358242 | None | None | N |
| R/T | 0.1601 | likely_benign | 0.144 | benign | 0.023 | Stabilizing | 0.801 | D | 0.518 | neutral | N | 0.405516734 | None | None | N |
| R/V | 0.2125 | likely_benign | 0.1869 | benign | 0.361 | Stabilizing | 0.974 | D | 0.433 | neutral | None | None | None | None | N |
| R/W | 0.169 | likely_benign | 0.1459 | benign | -0.396 | Destabilizing | 0.998 | D | 0.527 | neutral | None | None | None | None | N |
| R/Y | 0.2787 | likely_benign | 0.2302 | benign | 0.015 | Stabilizing | 0.991 | D | 0.478 | 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.