Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21300 | 64123;64124;64125 | chr2:178587313;178587312;178587311 | chr2:179452040;179452039;179452038 |
| N2AB | 19659 | 59200;59201;59202 | chr2:178587313;178587312;178587311 | chr2:179452040;179452039;179452038 |
| N2A | 18732 | 56419;56420;56421 | chr2:178587313;178587312;178587311 | chr2:179452040;179452039;179452038 |
| N2B | 12235 | 36928;36929;36930 | chr2:178587313;178587312;178587311 | chr2:179452040;179452039;179452038 |
| Novex-1 | 12360 | 37303;37304;37305 | chr2:178587313;178587312;178587311 | chr2:179452040;179452039;179452038 |
| Novex-2 | 12427 | 37504;37505;37506 | chr2:178587313;178587312;178587311 | chr2:179452040;179452039;179452038 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/N | None | None | 0.061 | N | 0.133 | 0.217 | 0.208816687407 | gnomAD-4.0.0 | 1.36909E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99709E-07 | 0 | 1.65772E-05 |
| H/R | rs757842155  |
-1.037 | 0.959 | N | 0.519 | 0.247 | 0.311079019809 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.69914E-04 | None | 0 | None | 0 | 0 | 0 |
| H/R | rs757842155 |
-1.037 | 0.959 | N | 0.519 | 0.247 | 0.311079019809 | gnomAD-4.0.0 | 3.42264E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.01374E-04 | None | 0 | 0 | 0 | 0 | 1.65777E-05 |
| H/Y | rs376033054 |
0.921 | 0.986 | N | 0.562 | 0.365 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| H/Y | rs376033054 |
0.921 | 0.986 | N | 0.562 | 0.365 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.84E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| H/Y | rs376033054 |
0.921 | 0.986 | N | 0.562 | 0.365 | None | gnomAD-4.0.0 | 1.86025E-06 | None | None | None | None | N | None | 2.67473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.0983E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.4365 | ambiguous | 0.4095 | ambiguous | -1.332 | Destabilizing | 0.759 | D | 0.511 | neutral | None | None | None | None | N |
| H/C | 0.1888 | likely_benign | 0.2063 | benign | -0.472 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| H/D | 0.4767 | ambiguous | 0.4454 | ambiguous | -1.017 | Destabilizing | 0.704 | D | 0.542 | neutral | N | 0.503280063 | None | None | N |
| H/E | 0.6738 | likely_pathogenic | 0.6477 | pathogenic | -0.869 | Destabilizing | 0.863 | D | 0.541 | neutral | None | None | None | None | N |
| H/F | 0.4898 | ambiguous | 0.4948 | ambiguous | 0.251 | Stabilizing | 0.997 | D | 0.618 | neutral | None | None | None | None | N |
| H/G | 0.2956 | likely_benign | 0.2764 | benign | -1.716 | Destabilizing | 0.863 | D | 0.504 | neutral | None | None | None | None | N |
| H/I | 0.843 | likely_pathogenic | 0.8333 | pathogenic | -0.234 | Destabilizing | 0.991 | D | 0.665 | neutral | None | None | None | None | N |
| H/K | 0.6241 | likely_pathogenic | 0.558 | ambiguous | -0.937 | Destabilizing | 0.939 | D | 0.579 | neutral | None | None | None | None | N |
| H/L | 0.4118 | ambiguous | 0.4142 | ambiguous | -0.234 | Destabilizing | 0.959 | D | 0.626 | neutral | N | 0.483129937 | None | None | N |
| H/M | 0.7468 | likely_pathogenic | 0.7365 | pathogenic | -0.392 | Destabilizing | 0.997 | D | 0.618 | neutral | None | None | None | None | N |
| H/N | 0.0965 | likely_benign | 0.1038 | benign | -1.237 | Destabilizing | 0.061 | N | 0.133 | neutral | N | 0.420701539 | None | None | N |
| H/P | 0.9633 | likely_pathogenic | 0.9655 | pathogenic | -0.585 | Destabilizing | 0.988 | D | 0.66 | neutral | N | 0.501741171 | None | None | N |
| H/Q | 0.3882 | ambiguous | 0.376 | ambiguous | -0.907 | Destabilizing | 0.959 | D | 0.575 | neutral | N | 0.468379817 | None | None | N |
| H/R | 0.2912 | likely_benign | 0.2653 | benign | -1.224 | Destabilizing | 0.959 | D | 0.519 | neutral | N | 0.496122017 | None | None | N |
| H/S | 0.21 | likely_benign | 0.205 | benign | -1.347 | Destabilizing | 0.2 | N | 0.215 | neutral | None | None | None | None | N |
| H/T | 0.4672 | ambiguous | 0.4382 | ambiguous | -1.099 | Destabilizing | 0.884 | D | 0.605 | neutral | None | None | None | None | N |
| H/V | 0.7309 | likely_pathogenic | 0.7112 | pathogenic | -0.585 | Destabilizing | 0.969 | D | 0.669 | neutral | None | None | None | None | N |
| H/W | 0.6533 | likely_pathogenic | 0.6468 | pathogenic | 0.683 | Stabilizing | 0.999 | D | 0.648 | neutral | None | None | None | None | N |
| H/Y | 0.1523 | likely_benign | 0.1648 | benign | 0.647 | Stabilizing | 0.986 | D | 0.562 | neutral | N | 0.48719589 | 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.