Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21604 | 65035;65036;65037 | chr2:178584831;178584830;178584829 | chr2:179449558;179449557;179449556 |
| N2AB | 19963 | 60112;60113;60114 | chr2:178584831;178584830;178584829 | chr2:179449558;179449557;179449556 |
| N2A | 19036 | 57331;57332;57333 | chr2:178584831;178584830;178584829 | chr2:179449558;179449557;179449556 |
| N2B | 12539 | 37840;37841;37842 | chr2:178584831;178584830;178584829 | chr2:179449558;179449557;179449556 |
| Novex-1 | 12664 | 38215;38216;38217 | chr2:178584831;178584830;178584829 | chr2:179449558;179449557;179449556 |
| Novex-2 | 12731 | 38416;38417;38418 | chr2:178584831;178584830;178584829 | chr2:179449558;179449557;179449556 |
| 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 | rs767011515  |
-0.683 | 0.417 | N | 0.35 | 0.161 | 0.37262878642 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/G | rs767011515 |
-0.683 | 0.417 | N | 0.35 | 0.161 | 0.37262878642 | gnomAD-4.0.0 | 1.36869E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79925E-06 | 0 | 0 |
| R/P | rs188996850 |
None | 0.836 | N | 0.456 | 0.263 | 0.393316636838 | gnomAD-4.0.0 | 1.36868E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.04236E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs188996850 |
0.052 | 0.005 | N | 0.227 | 0.083 | None | gnomAD-2.1.1 | 1.07279E-04 | None | None | None | None | N | None | 0 | 1.6977E-04 | None | 0 | 1.13064E-03 | None | 0 | None | 0 | 0 | 2.80978E-04 |
| R/Q | rs188996850 |
0.052 | 0.005 | N | 0.227 | 0.083 | None | gnomAD-3.1.2 | 2.56643E-04 | None | None | None | None | N | None | 0 | 2.36158E-03 | 0 | 0 | 5.83885E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs188996850 |
0.052 | 0.005 | N | 0.227 | 0.083 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 4.3E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs188996850 |
0.052 | 0.005 | N | 0.227 | 0.083 | None | gnomAD-4.0.0 | 5.95039E-05 | None | None | None | None | N | None | 2.66788E-05 | 9.83792E-04 | None | 0 | 3.79549E-04 | None | 0 | 0 | 5.08677E-06 | 0 | 1.92141E-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 | 0.3376 | likely_benign | 0.4937 | ambiguous | -0.268 | Destabilizing | 0.157 | N | 0.369 | neutral | None | None | None | None | N |
| R/C | 0.1694 | likely_benign | 0.2163 | benign | -0.197 | Destabilizing | 0.968 | D | 0.615 | neutral | None | None | None | None | N |
| R/D | 0.6157 | likely_pathogenic | 0.7409 | pathogenic | -0.17 | Destabilizing | 0.567 | D | 0.359 | neutral | None | None | None | None | N |
| R/E | 0.3446 | ambiguous | 0.4694 | ambiguous | -0.133 | Destabilizing | 0.157 | N | 0.336 | neutral | None | None | None | None | N |
| R/F | 0.5939 | likely_pathogenic | 0.7263 | pathogenic | -0.615 | Destabilizing | 0.89 | D | 0.541 | neutral | None | None | None | None | N |
| R/G | 0.221 | likely_benign | 0.3124 | benign | -0.434 | Destabilizing | 0.417 | N | 0.35 | neutral | N | 0.453965963 | None | None | N |
| R/H | 0.0903 | likely_benign | 0.1076 | benign | -0.896 | Destabilizing | 0.567 | D | 0.266 | neutral | None | None | None | None | N |
| R/I | 0.3801 | ambiguous | 0.5185 | ambiguous | 0.133 | Stabilizing | 0.726 | D | 0.535 | neutral | None | None | None | None | N |
| R/K | 0.1118 | likely_benign | 0.1235 | benign | -0.212 | Destabilizing | 0.072 | N | 0.347 | neutral | None | None | None | None | N |
| R/L | 0.2489 | likely_benign | 0.3581 | ambiguous | 0.133 | Stabilizing | 0.417 | N | 0.35 | neutral | N | 0.47859726 | None | None | N |
| R/M | 0.3137 | likely_benign | 0.4284 | ambiguous | 0.017 | Stabilizing | 0.909 | D | 0.362 | neutral | None | None | None | None | N |
| R/N | 0.4749 | ambiguous | 0.618 | pathogenic | 0.194 | Stabilizing | 0.567 | D | 0.27 | neutral | None | None | None | None | N |
| R/P | 0.808 | likely_pathogenic | 0.8779 | pathogenic | 0.018 | Stabilizing | 0.836 | D | 0.456 | neutral | N | 0.489332118 | None | None | N |
| R/Q | 0.0906 | likely_benign | 0.1166 | benign | -0.05 | Destabilizing | 0.005 | N | 0.227 | neutral | N | 0.48028856 | None | None | N |
| R/S | 0.3947 | ambiguous | 0.5463 | ambiguous | -0.269 | Destabilizing | 0.157 | N | 0.375 | neutral | None | None | None | None | N |
| R/T | 0.219 | likely_benign | 0.3252 | benign | -0.113 | Destabilizing | 0.272 | N | 0.351 | neutral | None | None | None | None | N |
| R/V | 0.4183 | ambiguous | 0.5557 | ambiguous | 0.018 | Stabilizing | 0.567 | D | 0.52 | neutral | None | None | None | None | N |
| R/W | 0.2191 | likely_benign | 0.283 | benign | -0.61 | Destabilizing | 0.968 | D | 0.635 | neutral | None | None | None | None | N |
| R/Y | 0.4413 | ambiguous | 0.5604 | ambiguous | -0.207 | Destabilizing | 0.726 | D | 0.457 | 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.