Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2508 | 7747;7748;7749 | chr2:178773534;178773533;178773532 | chr2:179638261;179638260;179638259 |
| N2AB | 2508 | 7747;7748;7749 | chr2:178773534;178773533;178773532 | chr2:179638261;179638260;179638259 |
| N2A | 2508 | 7747;7748;7749 | chr2:178773534;178773533;178773532 | chr2:179638261;179638260;179638259 |
| N2B | 2462 | 7609;7610;7611 | chr2:178773534;178773533;178773532 | chr2:179638261;179638260;179638259 |
| Novex-1 | 2462 | 7609;7610;7611 | chr2:178773534;178773533;178773532 | chr2:179638261;179638260;179638259 |
| Novex-2 | 2462 | 7609;7610;7611 | chr2:178773534;178773533;178773532 | chr2:179638261;179638260;179638259 |
| Novex-3 | 2508 | 7747;7748;7749 | chr2:178773534;178773533;178773532 | chr2:179638261;179638260;179638259 |
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/Q | None | None | 0.175 | N | 0.235 | 0.07 | 0.137902524267 | gnomAD-4.0.0 | 4.78873E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.9562E-05 | 1.65585E-05 |
| H/R | rs146970027  |
0.041 | 0.001 | N | 0.146 | 0.141 | None | gnomAD-2.1.1 | 5.0636E-04 | None | None | None | None | N | None | 8.01E-05 | 2.82E-05 | None | 1.93013E-04 | 0 | None | 0 | None | 2.11038E-03 | 6.13107E-04 | 8.31947E-04 |
| H/R | rs146970027 |
0.041 | 0.001 | N | 0.146 | 0.141 | None | gnomAD-3.1.2 | 3.81133E-04 | None | None | None | None | N | None | 1.44781E-04 | 0 | 0 | 5.76701E-04 | 0 | None | 1.60075E-03 | 0 | 4.70367E-04 | 0 | 4.77555E-04 |
| H/R | rs146970027 |
0.041 | 0.001 | N | 0.146 | 0.141 | None | gnomAD-4.0.0 | 6.26464E-04 | None | None | None | None | N | None | 1.06783E-04 | 0 | None | 2.02703E-04 | 0 | None | 1.99913E-03 | 0 | 7.07704E-04 | 0 | 5.44209E-04 |
| H/Y | None | None | None | N | 0.098 | 0.108 | 0.154104182512 | gnomAD-4.0.0 | 2.73642E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59726E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.33 | likely_benign | 0.3049 | benign | -0.107 | Destabilizing | 0.104 | N | 0.349 | neutral | None | None | None | None | N |
| H/C | 0.1682 | likely_benign | 0.1557 | benign | 0.452 | Stabilizing | 0.958 | D | 0.323 | neutral | None | None | None | None | N |
| H/D | 0.2973 | likely_benign | 0.2747 | benign | 0.152 | Stabilizing | 0.175 | N | 0.37 | neutral | N | 0.470006298 | None | None | N |
| H/E | 0.3406 | ambiguous | 0.3204 | benign | 0.182 | Stabilizing | 0.22 | N | 0.148 | neutral | None | None | None | None | N |
| H/F | 0.1694 | likely_benign | 0.1625 | benign | 0.471 | Stabilizing | None | N | 0.12 | neutral | None | None | None | None | N |
| H/G | 0.3834 | ambiguous | 0.3558 | ambiguous | -0.399 | Destabilizing | 0.22 | N | 0.345 | neutral | None | None | None | None | N |
| H/I | 0.3627 | ambiguous | 0.3359 | benign | 0.648 | Stabilizing | 0.22 | N | 0.384 | neutral | None | None | None | None | N |
| H/K | 0.2518 | likely_benign | 0.2374 | benign | -0.048 | Destabilizing | 0.124 | N | 0.303 | neutral | None | None | None | None | N |
| H/L | 0.1412 | likely_benign | 0.1324 | benign | 0.648 | Stabilizing | 0.042 | N | 0.342 | neutral | N | 0.461197284 | None | None | N |
| H/M | 0.438 | ambiguous | 0.4071 | ambiguous | 0.544 | Stabilizing | 0.859 | D | 0.331 | neutral | None | None | None | None | N |
| H/N | 0.1369 | likely_benign | 0.1248 | benign | 0.093 | Stabilizing | 0.175 | N | 0.184 | neutral | N | 0.475806543 | None | None | N |
| H/P | 0.6434 | likely_pathogenic | 0.6199 | pathogenic | 0.422 | Stabilizing | 0.822 | D | 0.373 | neutral | N | 0.50967633 | None | None | N |
| H/Q | 0.2053 | likely_benign | 0.1904 | benign | 0.178 | Stabilizing | 0.175 | N | 0.235 | neutral | N | 0.444863111 | None | None | N |
| H/R | 0.1135 | likely_benign | 0.1053 | benign | -0.462 | Destabilizing | 0.001 | N | 0.146 | neutral | N | 0.405487319 | None | None | N |
| H/S | 0.2593 | likely_benign | 0.2393 | benign | 0.015 | Stabilizing | 0.22 | N | 0.298 | neutral | None | None | None | None | N |
| H/T | 0.313 | likely_benign | 0.2826 | benign | 0.144 | Stabilizing | 0.22 | N | 0.355 | neutral | None | None | None | None | N |
| H/V | 0.2736 | likely_benign | 0.2572 | benign | 0.422 | Stabilizing | 0.22 | N | 0.367 | neutral | None | None | None | None | N |
| H/W | 0.2935 | likely_benign | 0.2899 | benign | 0.549 | Stabilizing | 0.667 | D | 0.33 | neutral | None | None | None | None | N |
| H/Y | 0.0651 | likely_benign | 0.062 | benign | 0.859 | Stabilizing | None | N | 0.098 | neutral | N | 0.425724825 | 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.