Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20132 | 60619;60620;60621 | chr2:178591331;178591330;178591329 | chr2:179456058;179456057;179456056 |
| N2AB | 18491 | 55696;55697;55698 | chr2:178591331;178591330;178591329 | chr2:179456058;179456057;179456056 |
| N2A | 17564 | 52915;52916;52917 | chr2:178591331;178591330;178591329 | chr2:179456058;179456057;179456056 |
| N2B | 11067 | 33424;33425;33426 | chr2:178591331;178591330;178591329 | chr2:179456058;179456057;179456056 |
| Novex-1 | 11192 | 33799;33800;33801 | chr2:178591331;178591330;178591329 | chr2:179456058;179456057;179456056 |
| Novex-2 | 11259 | 34000;34001;34002 | chr2:178591331;178591330;178591329 | chr2:179456058;179456057;179456056 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | None | None | 0.915 | N | 0.521 | 0.284 | 0.704619230643 | gnomAD-4.0.0 | 1.59223E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86028E-06 | 0 | 0 |
| F/L | rs1304980579  |
-0.425 | 0.027 | N | 0.409 | 0.152 | 0.441844919209 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs1304980579 |
-0.425 | 0.027 | N | 0.409 | 0.152 | 0.441844919209 | gnomAD-4.0.0 | 1.59225E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77331E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.4174 | ambiguous | 0.4196 | ambiguous | -1.212 | Destabilizing | 0.149 | N | 0.506 | neutral | None | None | None | None | N |
| F/C | 0.2326 | likely_benign | 0.2609 | benign | -0.511 | Destabilizing | 0.915 | D | 0.521 | neutral | N | 0.48940254 | None | None | N |
| F/D | 0.4998 | ambiguous | 0.5311 | ambiguous | 0.656 | Stabilizing | 0.235 | N | 0.516 | neutral | None | None | None | None | N |
| F/E | 0.6901 | likely_pathogenic | 0.7186 | pathogenic | 0.668 | Stabilizing | 0.149 | N | 0.519 | neutral | None | None | None | None | N |
| F/G | 0.586 | likely_pathogenic | 0.6118 | pathogenic | -1.444 | Destabilizing | 0.149 | N | 0.503 | neutral | None | None | None | None | N |
| F/H | 0.3345 | likely_benign | 0.3558 | ambiguous | 0.126 | Stabilizing | 0.38 | N | 0.509 | neutral | None | None | None | None | N |
| F/I | 0.1802 | likely_benign | 0.181 | benign | -0.585 | Destabilizing | 0.117 | N | 0.455 | neutral | N | 0.504390076 | None | None | N |
| F/K | 0.6674 | likely_pathogenic | 0.7109 | pathogenic | -0.335 | Destabilizing | 0.38 | N | 0.514 | neutral | None | None | None | None | N |
| F/L | 0.7821 | likely_pathogenic | 0.7734 | pathogenic | -0.585 | Destabilizing | 0.027 | N | 0.409 | neutral | N | 0.504216717 | None | None | N |
| F/M | 0.482 | ambiguous | 0.4734 | ambiguous | -0.506 | Destabilizing | 0.555 | D | 0.475 | neutral | None | None | None | None | N |
| F/N | 0.2942 | likely_benign | 0.331 | benign | -0.332 | Destabilizing | 0.002 | N | 0.404 | neutral | None | None | None | None | N |
| F/P | 0.9598 | likely_pathogenic | 0.9578 | pathogenic | -0.777 | Destabilizing | 0.791 | D | 0.533 | neutral | None | None | None | None | N |
| F/Q | 0.593 | likely_pathogenic | 0.6187 | pathogenic | -0.357 | Destabilizing | 0.555 | D | 0.54 | neutral | None | None | None | None | N |
| F/R | 0.553 | ambiguous | 0.5993 | pathogenic | 0.159 | Stabilizing | 0.38 | N | 0.539 | neutral | None | None | None | None | N |
| F/S | 0.2413 | likely_benign | 0.2457 | benign | -1.075 | Destabilizing | 0.117 | N | 0.494 | neutral | N | 0.434778062 | None | None | N |
| F/T | 0.2982 | likely_benign | 0.3092 | benign | -0.97 | Destabilizing | 0.149 | N | 0.523 | neutral | None | None | None | None | N |
| F/V | 0.181 | likely_benign | 0.1846 | benign | -0.777 | Destabilizing | 0.117 | N | 0.451 | neutral | N | 0.464178249 | None | None | N |
| F/W | 0.4744 | ambiguous | 0.4504 | ambiguous | -0.137 | Destabilizing | 0.555 | D | 0.491 | neutral | None | None | None | None | N |
| F/Y | 0.0673 | likely_benign | 0.074 | benign | -0.231 | Destabilizing | None | N | 0.137 | neutral | N | 0.454115971 | 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.