Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3988 | 12187;12188;12189 | chr2:178741271;178741270;178741269 | chr2:179605998;179605997;179605996 |
| N2AB | 3671 | 11236;11237;11238 | chr2:178741271;178741270;178741269 | chr2:179605998;179605997;179605996 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3625 | 11098;11099;11100 | chr2:178741271;178741270;178741269 | chr2:179605998;179605997;179605996 |
| Novex-1 | 3750 | 11473;11474;11475 | chr2:178741271;178741270;178741269 | chr2:179605998;179605997;179605996 |
| Novex-2 | 3817 | 11674;11675;11676 | chr2:178741271;178741270;178741269 | chr2:179605998;179605997;179605996 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/P | None | None | 0.202 | N | 0.57 | 0.32 | None | gnomAD-4.0.0 | 6.84195E-07 | None | None | None | None | N | None | 0 | 0 | None | 3.82673E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| H/R | rs1406738761  |
-0.684 | 0.025 | N | 0.413 | 0.181 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| H/R | rs1406738761 |
-0.684 | 0.025 | N | 0.413 | 0.181 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 4.78011E-04 |
| H/R | rs1406738761 |
-0.684 | 0.025 | N | 0.413 | 0.181 | None | gnomAD-4.0.0 | 6.19659E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.78052E-06 | 0 | 3.20215E-05 |
| H/Y | rs749409521 |
0.787 | None | N | 0.213 | 0.145 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| H/Y | rs749409521 |
0.787 | None | N | 0.213 | 0.145 | None | gnomAD-4.0.0 | 2.25786E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87817E-05 | 0 | 1.65656E-05 |
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 | 0.3067 | likely_benign | 0.2963 | benign | -0.602 | Destabilizing | 0.001 | N | 0.403 | neutral | None | None | None | None | N |
| H/C | 0.186 | likely_benign | 0.1705 | benign | -0.05 | Destabilizing | 0.001 | N | 0.458 | neutral | None | None | None | None | N |
| H/D | 0.1847 | likely_benign | 0.1828 | benign | -0.135 | Destabilizing | 0.025 | N | 0.477 | neutral | N | 0.491910118 | None | None | N |
| H/E | 0.2645 | likely_benign | 0.2502 | benign | -0.06 | Destabilizing | 0.033 | N | 0.338 | neutral | None | None | None | None | N |
| H/F | 0.4406 | ambiguous | 0.4152 | ambiguous | 0.319 | Stabilizing | 0.076 | N | 0.519 | neutral | None | None | None | None | N |
| H/G | 0.3106 | likely_benign | 0.2988 | benign | -0.94 | Destabilizing | 0.033 | N | 0.483 | neutral | None | None | None | None | N |
| H/I | 0.4154 | ambiguous | 0.387 | ambiguous | 0.307 | Stabilizing | 0.142 | N | 0.584 | neutral | None | None | None | None | N |
| H/K | 0.2882 | likely_benign | 0.2751 | benign | -0.508 | Destabilizing | 0.033 | N | 0.461 | neutral | None | None | None | None | N |
| H/L | 0.154 | likely_benign | 0.1472 | benign | 0.307 | Stabilizing | 0.025 | N | 0.526 | neutral | N | 0.505275243 | None | None | N |
| H/M | 0.5991 | likely_pathogenic | 0.5639 | ambiguous | 0.129 | Stabilizing | 0.54 | D | 0.594 | neutral | None | None | None | None | N |
| H/N | 0.097 | likely_benign | 0.0967 | benign | -0.534 | Destabilizing | None | N | 0.24 | neutral | N | 0.480249105 | None | None | N |
| H/P | 0.1458 | likely_benign | 0.1624 | benign | 0.027 | Stabilizing | 0.202 | N | 0.57 | neutral | N | 0.507370455 | None | None | N |
| H/Q | 0.1757 | likely_benign | 0.1663 | benign | -0.345 | Destabilizing | 0.001 | N | 0.247 | neutral | N | 0.478036529 | None | None | N |
| H/R | 0.1156 | likely_benign | 0.109 | benign | -0.927 | Destabilizing | 0.025 | N | 0.413 | neutral | N | 0.49943991 | None | None | N |
| H/S | 0.2179 | likely_benign | 0.2099 | benign | -0.658 | Destabilizing | 0.003 | N | 0.301 | neutral | None | None | None | None | N |
| H/T | 0.2811 | likely_benign | 0.2677 | benign | -0.473 | Destabilizing | 0.001 | N | 0.405 | neutral | None | None | None | None | N |
| H/V | 0.3462 | ambiguous | 0.3168 | benign | 0.027 | Stabilizing | 0.064 | N | 0.532 | neutral | None | None | None | None | N |
| H/W | 0.4689 | ambiguous | 0.4381 | ambiguous | 0.567 | Stabilizing | 0.816 | D | 0.589 | neutral | None | None | None | None | N |
| H/Y | 0.1177 | likely_benign | 0.1126 | benign | 0.75 | Stabilizing | None | N | 0.213 | neutral | N | 0.49740467 | 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.