Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26698 | 80317;80318;80319 | chr2:178566040;178566039;178566038 | chr2:179430767;179430766;179430765 |
| N2AB | 25057 | 75394;75395;75396 | chr2:178566040;178566039;178566038 | chr2:179430767;179430766;179430765 |
| N2A | 24130 | 72613;72614;72615 | chr2:178566040;178566039;178566038 | chr2:179430767;179430766;179430765 |
| N2B | 17633 | 53122;53123;53124 | chr2:178566040;178566039;178566038 | chr2:179430767;179430766;179430765 |
| Novex-1 | 17758 | 53497;53498;53499 | chr2:178566040;178566039;178566038 | chr2:179430767;179430766;179430765 |
| Novex-2 | 17825 | 53698;53699;53700 | chr2:178566040;178566039;178566038 | chr2:179430767;179430766;179430765 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/V | rs368085497  |
0.305 | 0.994 | N | 0.591 | 0.499 | None | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| D/V | rs368085497 |
0.305 | 0.994 | N | 0.591 | 0.499 | None | gnomAD-4.0.0 | 1.36866E-05 | None | None | None | None | N | None | 2.99007E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.70925E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2709 | likely_benign | 0.299 | benign | -0.195 | Destabilizing | 0.961 | D | 0.487 | neutral | N | 0.471991122 | None | None | N |
| D/C | 0.6898 | likely_pathogenic | 0.6909 | pathogenic | -0.062 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| D/E | 0.1739 | likely_benign | 0.1971 | benign | -0.775 | Destabilizing | 0.122 | N | 0.102 | neutral | N | 0.459588001 | None | None | N |
| D/F | 0.6461 | likely_pathogenic | 0.6566 | pathogenic | -0.457 | Destabilizing | 0.999 | D | 0.611 | neutral | None | None | None | None | N |
| D/G | 0.1767 | likely_benign | 0.1817 | benign | -0.477 | Destabilizing | 0.961 | D | 0.441 | neutral | N | 0.498549034 | None | None | N |
| D/H | 0.3893 | ambiguous | 0.4288 | ambiguous | -0.936 | Destabilizing | 0.994 | D | 0.481 | neutral | D | 0.523138047 | None | None | N |
| D/I | 0.5106 | ambiguous | 0.5412 | ambiguous | 0.515 | Stabilizing | 0.999 | D | 0.597 | neutral | None | None | None | None | N |
| D/K | 0.5854 | likely_pathogenic | 0.6318 | pathogenic | -0.375 | Destabilizing | 0.97 | D | 0.433 | neutral | None | None | None | None | N |
| D/L | 0.545 | ambiguous | 0.5759 | pathogenic | 0.515 | Stabilizing | 0.996 | D | 0.593 | neutral | None | None | None | None | N |
| D/M | 0.6581 | likely_pathogenic | 0.6942 | pathogenic | 0.937 | Stabilizing | 1.0 | D | 0.606 | neutral | None | None | None | None | N |
| D/N | 0.1011 | likely_benign | 0.1059 | benign | -0.534 | Destabilizing | 0.248 | N | 0.264 | neutral | N | 0.472322438 | None | None | N |
| D/P | 0.9198 | likely_pathogenic | 0.9304 | pathogenic | 0.304 | Stabilizing | 0.999 | D | 0.465 | neutral | None | None | None | None | N |
| D/Q | 0.4274 | ambiguous | 0.4818 | ambiguous | -0.454 | Destabilizing | 0.991 | D | 0.444 | neutral | None | None | None | None | N |
| D/R | 0.6338 | likely_pathogenic | 0.6783 | pathogenic | -0.446 | Destabilizing | 0.991 | D | 0.504 | neutral | None | None | None | None | N |
| D/S | 0.1556 | likely_benign | 0.1675 | benign | -0.759 | Destabilizing | 0.97 | D | 0.436 | neutral | None | None | None | None | N |
| D/T | 0.2489 | likely_benign | 0.2669 | benign | -0.543 | Destabilizing | 0.97 | D | 0.459 | neutral | None | None | None | None | N |
| D/V | 0.3472 | ambiguous | 0.3693 | ambiguous | 0.304 | Stabilizing | 0.994 | D | 0.591 | neutral | N | 0.498742658 | None | None | N |
| D/W | 0.918 | likely_pathogenic | 0.9214 | pathogenic | -0.557 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | N |
| D/Y | 0.3084 | likely_benign | 0.3102 | benign | -0.298 | Destabilizing | 0.998 | D | 0.611 | neutral | N | 0.516593423 | 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.