Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32588 | 97987;97988;97989 | chr2:178541315;178541314;178541313 | chr2:179406042;179406041;179406040 |
| N2AB | 30947 | 93064;93065;93066 | chr2:178541315;178541314;178541313 | chr2:179406042;179406041;179406040 |
| N2A | 30020 | 90283;90284;90285 | chr2:178541315;178541314;178541313 | chr2:179406042;179406041;179406040 |
| N2B | 23523 | 70792;70793;70794 | chr2:178541315;178541314;178541313 | chr2:179406042;179406041;179406040 |
| Novex-1 | 23648 | 71167;71168;71169 | chr2:178541315;178541314;178541313 | chr2:179406042;179406041;179406040 |
| Novex-2 | 23715 | 71368;71369;71370 | chr2:178541315;178541314;178541313 | chr2:179406042;179406041;179406040 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 0.002 | N | 0.442 | 0.129 | 0.16115917748 | gnomAD-4.0.0 | 7.18103E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32987E-07 | 0 | 0 |
| P/L | rs1487598622  |
-0.568 | 0.651 | N | 0.725 | 0.236 | 0.488548280593 | gnomAD-2.1.1 | 6.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 8.51E-05 | None | 0 | None | 0 | 0 | 0 |
| P/L | rs1487598622 |
-0.568 | 0.651 | N | 0.725 | 0.236 | 0.488548280593 | gnomAD-4.0.0 | 1.79193E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.05736E-05 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | None | None | 0.01 | N | 0.433 | 0.145 | 0.163833314356 | gnomAD-4.0.0 | 1.43621E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.86597E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0707 | likely_benign | 0.0726 | benign | -1.074 | Destabilizing | 0.002 | N | 0.442 | neutral | N | 0.463548239 | None | None | N |
| P/C | 0.3504 | ambiguous | 0.3883 | ambiguous | -0.719 | Destabilizing | 0.985 | D | 0.748 | deleterious | None | None | None | None | N |
| P/D | 0.571 | likely_pathogenic | 0.6508 | pathogenic | -0.413 | Destabilizing | 0.553 | D | 0.7 | prob.delet. | None | None | None | None | N |
| P/E | 0.3333 | likely_benign | 0.4078 | ambiguous | -0.442 | Destabilizing | 0.712 | D | 0.705 | prob.delet. | None | None | None | None | N |
| P/F | 0.4144 | ambiguous | 0.4686 | ambiguous | -0.857 | Destabilizing | 0.946 | D | 0.765 | deleterious | None | None | None | None | N |
| P/G | 0.3019 | likely_benign | 0.3219 | benign | -1.335 | Destabilizing | 0.338 | N | 0.61 | neutral | None | None | None | None | N |
| P/H | 0.2505 | likely_benign | 0.2956 | benign | -0.721 | Destabilizing | 0.93 | D | 0.683 | prob.neutral | N | 0.493547963 | None | None | N |
| P/I | 0.1797 | likely_benign | 0.2077 | benign | -0.485 | Destabilizing | 0.897 | D | 0.786 | deleterious | None | None | None | None | N |
| P/K | 0.3429 | ambiguous | 0.4186 | ambiguous | -0.766 | Destabilizing | 0.712 | D | 0.692 | prob.delet. | None | None | None | None | N |
| P/L | 0.1045 | likely_benign | 0.1296 | benign | -0.485 | Destabilizing | 0.651 | D | 0.725 | deleterious | N | 0.467085916 | None | None | N |
| P/M | 0.2448 | likely_benign | 0.2776 | benign | -0.467 | Destabilizing | 0.995 | D | 0.682 | prob.neutral | None | None | None | None | N |
| P/N | 0.3287 | likely_benign | 0.3811 | ambiguous | -0.521 | Destabilizing | 0.014 | N | 0.503 | neutral | None | None | None | None | N |
| P/Q | 0.1846 | likely_benign | 0.2203 | benign | -0.68 | Destabilizing | 0.946 | D | 0.795 | deleterious | None | None | None | None | N |
| P/R | 0.253 | likely_benign | 0.3176 | benign | -0.275 | Destabilizing | 0.868 | D | 0.731 | deleterious | N | 0.496003498 | None | None | N |
| P/S | 0.1331 | likely_benign | 0.1416 | benign | -1.053 | Destabilizing | 0.01 | N | 0.433 | neutral | N | 0.500815761 | None | None | N |
| P/T | 0.1026 | likely_benign | 0.1153 | benign | -0.966 | Destabilizing | 0.278 | N | 0.687 | prob.delet. | N | 0.515457139 | None | None | N |
| P/V | 0.1334 | likely_benign | 0.1498 | benign | -0.645 | Destabilizing | 0.553 | D | 0.678 | prob.neutral | None | None | None | None | N |
| P/W | 0.605 | likely_pathogenic | 0.6818 | pathogenic | -0.964 | Destabilizing | 0.995 | D | 0.761 | deleterious | None | None | None | None | N |
| P/Y | 0.4351 | ambiguous | 0.4937 | ambiguous | -0.678 | Destabilizing | 0.982 | D | 0.772 | deleterious | 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.