Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14069 | 42430;42431;42432 | chr2:178634576;178634575;178634574 | chr2:179499303;179499302;179499301 |
| N2AB | 12428 | 37507;37508;37509 | chr2:178634576;178634575;178634574 | chr2:179499303;179499302;179499301 |
| N2A | 11501 | 34726;34727;34728 | chr2:178634576;178634575;178634574 | chr2:179499303;179499302;179499301 |
| N2B | 5004 | 15235;15236;15237 | chr2:178634576;178634575;178634574 | chr2:179499303;179499302;179499301 |
| Novex-1 | 5129 | 15610;15611;15612 | chr2:178634576;178634575;178634574 | chr2:179499303;179499302;179499301 |
| Novex-2 | 5196 | 15811;15812;15813 | chr2:178634576;178634575;178634574 | chr2:179499303;179499302;179499301 |
| 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/Q | rs544852574  |
-0.088 | 0.985 | N | 0.419 | 0.267 | 0.146414634003 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 6.46E-05 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/Q | rs544852574 |
-0.088 | 0.985 | N | 0.419 | 0.267 | 0.146414634003 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs544852574 |
-0.088 | 0.985 | N | 0.419 | 0.267 | 0.146414634003 | gnomAD-4.0.0 | 8.67833E-06 | None | None | None | None | N | None | 5.34316E-05 | 1.66744E-05 | None | 0 | 0 | None | 0 | 0 | 6.78251E-06 | 1.09827E-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 | 0.6598 | likely_pathogenic | 0.745 | pathogenic | -0.15 | Destabilizing | 0.079 | N | 0.236 | neutral | None | None | None | None | N |
| R/C | 0.3159 | likely_benign | 0.3936 | ambiguous | -0.219 | Destabilizing | 0.999 | D | 0.364 | neutral | None | None | None | None | N |
| R/D | 0.8387 | likely_pathogenic | 0.8776 | pathogenic | -0.049 | Destabilizing | 0.969 | D | 0.358 | neutral | None | None | None | None | N |
| R/E | 0.5153 | ambiguous | 0.5977 | pathogenic | 0.033 | Stabilizing | 0.863 | D | 0.345 | neutral | None | None | None | None | N |
| R/F | 0.7255 | likely_pathogenic | 0.7988 | pathogenic | -0.272 | Destabilizing | 0.997 | D | 0.365 | neutral | None | None | None | None | N |
| R/G | 0.3915 | ambiguous | 0.4884 | ambiguous | -0.385 | Destabilizing | 0.967 | D | 0.378 | neutral | N | 0.425956527 | None | None | N |
| R/H | 0.1509 | likely_benign | 0.1815 | benign | -0.898 | Destabilizing | 0.997 | D | 0.377 | neutral | None | None | None | None | N |
| R/I | 0.5095 | ambiguous | 0.6235 | pathogenic | 0.444 | Stabilizing | 0.991 | D | 0.381 | neutral | None | None | None | None | N |
| R/K | 0.1574 | likely_benign | 0.1858 | benign | -0.218 | Destabilizing | 0.079 | N | 0.193 | neutral | None | None | None | None | N |
| R/L | 0.4225 | ambiguous | 0.516 | ambiguous | 0.444 | Stabilizing | 0.967 | D | 0.385 | neutral | N | 0.429276145 | None | None | N |
| R/M | 0.4573 | ambiguous | 0.5611 | ambiguous | 0.028 | Stabilizing | 0.997 | D | 0.361 | neutral | None | None | None | None | N |
| R/N | 0.7244 | likely_pathogenic | 0.7923 | pathogenic | 0.109 | Stabilizing | 0.969 | D | 0.386 | neutral | None | None | None | None | N |
| R/P | 0.9268 | likely_pathogenic | 0.9556 | pathogenic | 0.268 | Stabilizing | 0.995 | D | 0.351 | neutral | N | 0.44689616 | None | None | N |
| R/Q | 0.1362 | likely_benign | 0.1637 | benign | -0.011 | Destabilizing | 0.985 | D | 0.419 | neutral | N | 0.403905939 | None | None | N |
| R/S | 0.6881 | likely_pathogenic | 0.7598 | pathogenic | -0.336 | Destabilizing | 0.759 | D | 0.365 | neutral | None | None | None | None | N |
| R/T | 0.4976 | ambiguous | 0.5985 | pathogenic | -0.103 | Destabilizing | 0.939 | D | 0.389 | neutral | None | None | None | None | N |
| R/V | 0.6371 | likely_pathogenic | 0.7176 | pathogenic | 0.268 | Stabilizing | 0.939 | D | 0.411 | neutral | None | None | None | None | N |
| R/W | 0.3051 | likely_benign | 0.3848 | ambiguous | -0.224 | Destabilizing | 0.999 | D | 0.483 | neutral | None | None | None | None | N |
| R/Y | 0.5582 | ambiguous | 0.6225 | pathogenic | 0.161 | Stabilizing | 0.997 | D | 0.371 | 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.