Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20365 | 61318;61319;61320 | chr2:178590632;178590631;178590630 | chr2:179455359;179455358;179455357 |
| N2AB | 18724 | 56395;56396;56397 | chr2:178590632;178590631;178590630 | chr2:179455359;179455358;179455357 |
| N2A | 17797 | 53614;53615;53616 | chr2:178590632;178590631;178590630 | chr2:179455359;179455358;179455357 |
| N2B | 11300 | 34123;34124;34125 | chr2:178590632;178590631;178590630 | chr2:179455359;179455358;179455357 |
| Novex-1 | 11425 | 34498;34499;34500 | chr2:178590632;178590631;178590630 | chr2:179455359;179455358;179455357 |
| Novex-2 | 11492 | 34699;34700;34701 | chr2:178590632;178590631;178590630 | chr2:179455359;179455358;179455357 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs750381165  |
-1.795 | 0.976 | N | 0.587 | 0.231 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 1.65385E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs750381165 |
-1.795 | 0.976 | N | 0.587 | 0.231 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs750381165 |
-1.795 | 0.976 | N | 0.587 | 0.231 | None | gnomAD-4.0.0 | 4.95983E-06 | None | None | None | None | N | None | 1.06863E-04 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5413 | ambiguous | 0.5781 | pathogenic | -1.013 | Destabilizing | 1.0 | D | 0.7 | prob.delet. | None | None | None | None | N |
| A/D | 0.9805 | likely_pathogenic | 0.9862 | pathogenic | -1.505 | Destabilizing | 0.993 | D | 0.635 | neutral | N | 0.49474778 | None | None | N |
| A/E | 0.9685 | likely_pathogenic | 0.9734 | pathogenic | -1.592 | Destabilizing | 0.995 | D | 0.678 | prob.neutral | None | None | None | None | N |
| A/F | 0.7837 | likely_pathogenic | 0.8035 | pathogenic | -1.224 | Destabilizing | 0.998 | D | 0.675 | prob.neutral | None | None | None | None | N |
| A/G | 0.4179 | ambiguous | 0.4672 | ambiguous | -1.06 | Destabilizing | 0.976 | D | 0.485 | neutral | N | 0.47324971 | None | None | N |
| A/H | 0.9759 | likely_pathogenic | 0.9825 | pathogenic | -1.122 | Destabilizing | 1.0 | D | 0.685 | prob.delet. | None | None | None | None | N |
| A/I | 0.3939 | ambiguous | 0.406 | ambiguous | -0.565 | Destabilizing | 0.998 | D | 0.661 | prob.neutral | None | None | None | None | N |
| A/K | 0.9893 | likely_pathogenic | 0.9919 | pathogenic | -1.116 | Destabilizing | 0.995 | D | 0.677 | prob.neutral | None | None | None | None | N |
| A/L | 0.3707 | ambiguous | 0.3942 | ambiguous | -0.565 | Destabilizing | 0.982 | D | 0.619 | neutral | None | None | None | None | N |
| A/M | 0.4954 | ambiguous | 0.4907 | ambiguous | -0.428 | Destabilizing | 1.0 | D | 0.661 | prob.neutral | None | None | None | None | N |
| A/N | 0.903 | likely_pathogenic | 0.9276 | pathogenic | -0.839 | Destabilizing | 0.998 | D | 0.683 | prob.neutral | None | None | None | None | N |
| A/P | 0.3814 | ambiguous | 0.5122 | ambiguous | -0.633 | Destabilizing | 0.026 | N | 0.443 | neutral | N | 0.511349681 | None | None | N |
| A/Q | 0.9477 | likely_pathogenic | 0.9559 | pathogenic | -1.138 | Destabilizing | 0.998 | D | 0.647 | neutral | None | None | None | None | N |
| A/R | 0.9711 | likely_pathogenic | 0.9764 | pathogenic | -0.654 | Destabilizing | 0.998 | D | 0.687 | prob.delet. | None | None | None | None | N |
| A/S | 0.3069 | likely_benign | 0.3229 | benign | -1.091 | Destabilizing | 0.976 | D | 0.515 | neutral | N | 0.464108677 | None | None | N |
| A/T | 0.3208 | likely_benign | 0.3607 | ambiguous | -1.105 | Destabilizing | 0.976 | D | 0.587 | neutral | N | 0.477909111 | None | None | N |
| A/V | 0.1966 | likely_benign | 0.2167 | benign | -0.633 | Destabilizing | 0.976 | D | 0.557 | neutral | N | 0.465729247 | None | None | N |
| A/W | 0.9845 | likely_pathogenic | 0.9881 | pathogenic | -1.438 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| A/Y | 0.9333 | likely_pathogenic | 0.9453 | pathogenic | -1.078 | Destabilizing | 0.998 | D | 0.674 | prob.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.