Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29973 | 90142;90143;90144 | chr2:178552983;178552982;178552981 | chr2:179417710;179417709;179417708 |
| N2AB | 28332 | 85219;85220;85221 | chr2:178552983;178552982;178552981 | chr2:179417710;179417709;179417708 |
| N2A | 27405 | 82438;82439;82440 | chr2:178552983;178552982;178552981 | chr2:179417710;179417709;179417708 |
| N2B | 20908 | 62947;62948;62949 | chr2:178552983;178552982;178552981 | chr2:179417710;179417709;179417708 |
| Novex-1 | 21033 | 63322;63323;63324 | chr2:178552983;178552982;178552981 | chr2:179417710;179417709;179417708 |
| Novex-2 | 21100 | 63523;63524;63525 | chr2:178552983;178552982;178552981 | chr2:179417710;179417709;179417708 |
| 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 | rs1183482452  |
-1.527 | None | N | 0.15 | 0.111 | 0.21279746466 | gnomAD-2.1.1 | 7.17E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 7.83E-06 | 0 |
| R/K | rs1183482452 |
-1.527 | None | N | 0.15 | 0.111 | 0.21279746466 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/K | rs1183482452 |
-1.527 | None | N | 0.15 | 0.111 | 0.21279746466 | gnomAD-4.0.0 | 1.86077E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.6952E-06 | 1.09794E-05 | 0 |
| R/T | rs1183482452 |
None | 0.117 | N | 0.449 | 0.407 | 0.294918367191 | gnomAD-4.0.0 | 2.73955E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.63747E-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 | 0.9812 | likely_pathogenic | 0.9618 | pathogenic | -2.349 | Highly Destabilizing | 0.035 | N | 0.45 | neutral | None | None | None | None | N |
| R/C | 0.7463 | likely_pathogenic | 0.6373 | pathogenic | -2.019 | Highly Destabilizing | 0.935 | D | 0.653 | neutral | None | None | None | None | N |
| R/D | 0.998 | likely_pathogenic | 0.996 | pathogenic | -1.011 | Destabilizing | 0.149 | N | 0.554 | neutral | None | None | None | None | N |
| R/E | 0.9728 | likely_pathogenic | 0.9537 | pathogenic | -0.796 | Destabilizing | 0.035 | N | 0.462 | neutral | None | None | None | None | N |
| R/F | 0.9899 | likely_pathogenic | 0.9796 | pathogenic | -1.598 | Destabilizing | 0.791 | D | 0.643 | neutral | None | None | None | None | N |
| R/G | 0.9669 | likely_pathogenic | 0.9296 | pathogenic | -2.672 | Highly Destabilizing | 0.117 | N | 0.509 | neutral | N | 0.518025455 | None | None | N |
| R/H | 0.6771 | likely_pathogenic | 0.5428 | ambiguous | -2.395 | Highly Destabilizing | 0.555 | D | 0.429 | neutral | None | None | None | None | N |
| R/I | 0.9732 | likely_pathogenic | 0.9451 | pathogenic | -1.395 | Destabilizing | 0.484 | N | 0.63 | neutral | D | 0.526165756 | None | None | N |
| R/K | 0.2496 | likely_benign | 0.1618 | benign | -1.31 | Destabilizing | None | N | 0.15 | neutral | N | 0.49625809 | None | None | N |
| R/L | 0.9428 | likely_pathogenic | 0.8983 | pathogenic | -1.395 | Destabilizing | 0.149 | N | 0.509 | neutral | None | None | None | None | N |
| R/M | 0.9356 | likely_pathogenic | 0.8631 | pathogenic | -1.798 | Destabilizing | 0.791 | D | 0.509 | neutral | None | None | None | None | N |
| R/N | 0.9919 | likely_pathogenic | 0.9856 | pathogenic | -1.293 | Destabilizing | 0.149 | N | 0.43 | neutral | None | None | None | None | N |
| R/P | 0.999 | likely_pathogenic | 0.9978 | pathogenic | -1.706 | Destabilizing | 0.555 | D | 0.557 | neutral | None | None | None | None | N |
| R/Q | 0.5235 | ambiguous | 0.386 | ambiguous | -1.227 | Destabilizing | 0.081 | N | 0.458 | neutral | None | None | None | None | N |
| R/S | 0.9932 | likely_pathogenic | 0.985 | pathogenic | -2.288 | Highly Destabilizing | 0.062 | N | 0.454 | neutral | N | 0.491283465 | None | None | N |
| R/T | 0.9839 | likely_pathogenic | 0.9626 | pathogenic | -1.864 | Destabilizing | 0.117 | N | 0.449 | neutral | N | 0.521139327 | None | None | N |
| R/V | 0.9767 | likely_pathogenic | 0.9556 | pathogenic | -1.706 | Destabilizing | 0.38 | N | 0.59 | neutral | None | None | None | None | N |
| R/W | 0.9082 | likely_pathogenic | 0.8218 | pathogenic | -1.03 | Destabilizing | 0.935 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/Y | 0.9628 | likely_pathogenic | 0.9308 | pathogenic | -0.956 | Destabilizing | 0.555 | D | 0.599 | 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.