Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30944 | 93055;93056;93057 | chr2:178548796;178548795;178548794 | chr2:179413523;179413522;179413521 |
| N2AB | 29303 | 88132;88133;88134 | chr2:178548796;178548795;178548794 | chr2:179413523;179413522;179413521 |
| N2A | 28376 | 85351;85352;85353 | chr2:178548796;178548795;178548794 | chr2:179413523;179413522;179413521 |
| N2B | 21879 | 65860;65861;65862 | chr2:178548796;178548795;178548794 | chr2:179413523;179413522;179413521 |
| Novex-1 | 22004 | 66235;66236;66237 | chr2:178548796;178548795;178548794 | chr2:179413523;179413522;179413521 |
| Novex-2 | 22071 | 66436;66437;66438 | chr2:178548796;178548795;178548794 | chr2:179413523;179413522;179413521 |
| 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/C | rs1393282264  |
-0.25 | 1.0 | N | 0.478 | 0.452 | 0.57026793815 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/C | rs1393282264 |
-0.25 | 1.0 | N | 0.478 | 0.452 | 0.57026793815 | gnomAD-4.0.0 | 8.90155E-06 | None | None | None | None | I | None | 0 | 2.23634E-05 | None | 0 | 2.51991E-05 | None | 0 | 0 | 8.99476E-06 | 1.15934E-05 | 0 |
| R/H | rs755972883 |
-0.852 | 0.169 | N | 0.321 | 0.218 | None | gnomAD-2.1.1 | 1.21749E-04 | None | None | None | None | I | None | 4.13E-05 | 5.66E-05 | None | 0 | 0 | None | 0 | None | 9.50728E-04 | 6.25E-05 | 0 |
| R/H | rs755972883 |
-0.852 | 0.169 | N | 0.321 | 0.218 | None | gnomAD-3.1.2 | 9.2E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.42329E-04 | 0 | 5.88E-05 | 0 | 0 |
| R/H | rs755972883 |
-0.852 | 0.169 | N | 0.321 | 0.218 | None | gnomAD-4.0.0 | 5.9536E-05 | None | None | None | None | I | None | 0 | 3.33378E-05 | None | 0 | 0 | None | 6.04903E-04 | 0 | 4.57716E-05 | 1.09784E-05 | 1.60118E-05 |
| R/S | rs1393282264 |
None | 0.858 | N | 0.5 | 0.296 | 0.305410167561 | gnomAD-4.0.0 | 2.0542E-06 | None | None | None | None | I | None | 0 | 6.70901E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.6463 | likely_pathogenic | 0.5824 | pathogenic | -0.207 | Destabilizing | 0.863 | D | 0.465 | neutral | None | None | None | None | I |
| R/C | 0.2167 | likely_benign | 0.1749 | benign | -0.349 | Destabilizing | 1.0 | D | 0.478 | neutral | N | 0.487065232 | None | None | I |
| R/D | 0.8004 | likely_pathogenic | 0.771 | pathogenic | 0.023 | Stabilizing | 0.969 | D | 0.543 | neutral | None | None | None | None | I |
| R/E | 0.5776 | likely_pathogenic | 0.5319 | ambiguous | 0.118 | Stabilizing | 0.863 | D | 0.511 | neutral | None | None | None | None | I |
| R/F | 0.7053 | likely_pathogenic | 0.6267 | pathogenic | -0.275 | Destabilizing | 0.991 | D | 0.507 | neutral | None | None | None | None | I |
| R/G | 0.5338 | ambiguous | 0.4541 | ambiguous | -0.453 | Destabilizing | 0.983 | D | 0.539 | neutral | N | 0.498168048 | None | None | I |
| R/H | 0.1145 | likely_benign | 0.1006 | benign | -0.892 | Destabilizing | 0.169 | N | 0.321 | neutral | N | 0.463338663 | None | None | I |
| R/I | 0.4337 | ambiguous | 0.3794 | ambiguous | 0.42 | Stabilizing | 0.982 | D | 0.517 | neutral | None | None | None | None | I |
| R/K | 0.1902 | likely_benign | 0.1771 | benign | -0.241 | Destabilizing | 0.079 | N | 0.271 | neutral | None | None | None | None | I |
| R/L | 0.3777 | ambiguous | 0.336 | benign | 0.42 | Stabilizing | 0.967 | D | 0.541 | neutral | N | 0.513157835 | None | None | I |
| R/M | 0.5064 | ambiguous | 0.4357 | ambiguous | -0.066 | Destabilizing | 0.997 | D | 0.516 | neutral | None | None | None | None | I |
| R/N | 0.6712 | likely_pathogenic | 0.6278 | pathogenic | 0.017 | Stabilizing | 0.939 | D | 0.517 | neutral | None | None | None | None | I |
| R/P | 0.9308 | likely_pathogenic | 0.9154 | pathogenic | 0.233 | Stabilizing | 0.998 | D | 0.522 | neutral | N | 0.498168048 | None | None | I |
| R/Q | 0.1406 | likely_benign | 0.1257 | benign | -0.074 | Destabilizing | 0.939 | D | 0.503 | neutral | None | None | None | None | I |
| R/S | 0.6017 | likely_pathogenic | 0.5412 | ambiguous | -0.473 | Destabilizing | 0.858 | D | 0.5 | neutral | N | 0.451057305 | None | None | I |
| R/T | 0.3487 | ambiguous | 0.2923 | benign | -0.218 | Destabilizing | 0.079 | N | 0.301 | neutral | None | None | None | None | I |
| R/V | 0.5049 | ambiguous | 0.4521 | ambiguous | 0.233 | Stabilizing | 0.939 | D | 0.543 | neutral | None | None | None | None | I |
| R/W | 0.3105 | likely_benign | 0.2548 | benign | -0.201 | Destabilizing | 0.999 | D | 0.488 | neutral | None | None | None | None | I |
| R/Y | 0.4927 | ambiguous | 0.4385 | ambiguous | 0.176 | Stabilizing | 0.982 | D | 0.515 | neutral | None | None | None | None | I |
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.