Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3392 | 10399;10400;10401 | chr2:178759113;178759112;178759111 | chr2:179623840;179623839;179623838 |
| N2AB | 3392 | 10399;10400;10401 | chr2:178759113;178759112;178759111 | chr2:179623840;179623839;179623838 |
| N2A | 3392 | 10399;10400;10401 | chr2:178759113;178759112;178759111 | chr2:179623840;179623839;179623838 |
| N2B | 3346 | 10261;10262;10263 | chr2:178759113;178759112;178759111 | chr2:179623840;179623839;179623838 |
| Novex-1 | 3346 | 10261;10262;10263 | chr2:178759113;178759112;178759111 | chr2:179623840;179623839;179623838 |
| Novex-2 | 3346 | 10261;10262;10263 | chr2:178759113;178759112;178759111 | chr2:179623840;179623839;179623838 |
| Novex-3 | 3392 | 10399;10400;10401 | chr2:178759113;178759112;178759111 | chr2:179623840;179623839;179623838 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs755671177  |
-1.057 | 0.704 | N | 0.435 | 0.344 | 0.507510703362 | gnomAD-2.1.1 | 1.6E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 9.24E-05 | 8.84E-06 | 1.63613E-04 |
| M/I | rs755671177 |
-1.057 | 0.704 | N | 0.435 | 0.344 | 0.507510703362 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 1.47E-05 | 0 | 0 |
| M/I | rs755671177 |
-1.057 | 0.704 | N | 0.435 | 0.344 | 0.507510703362 | gnomAD-4.0.0 | 2.73646E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59732E-06 | 0 | 0 |
| M/K | None | None | 0.986 | D | 0.483 | 0.765 | 0.765320684573 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.7729 | likely_pathogenic | 0.8211 | pathogenic | -2.087 | Highly Destabilizing | 0.863 | D | 0.417 | neutral | None | None | None | None | N |
| M/C | 0.9275 | likely_pathogenic | 0.9264 | pathogenic | -1.545 | Destabilizing | 0.999 | D | 0.509 | neutral | None | None | None | None | N |
| M/D | 0.9663 | likely_pathogenic | 0.9746 | pathogenic | -0.871 | Destabilizing | 0.997 | D | 0.572 | neutral | None | None | None | None | N |
| M/E | 0.7485 | likely_pathogenic | 0.7923 | pathogenic | -0.765 | Destabilizing | 0.997 | D | 0.541 | neutral | None | None | None | None | N |
| M/F | 0.5015 | ambiguous | 0.5359 | ambiguous | -0.807 | Destabilizing | 0.991 | D | 0.465 | neutral | None | None | None | None | N |
| M/G | 0.9217 | likely_pathogenic | 0.9346 | pathogenic | -2.479 | Highly Destabilizing | 0.99 | D | 0.557 | neutral | None | None | None | None | N |
| M/H | 0.8418 | likely_pathogenic | 0.8535 | pathogenic | -1.57 | Destabilizing | 0.999 | D | 0.555 | neutral | None | None | None | None | N |
| M/I | 0.4466 | ambiguous | 0.5388 | ambiguous | -1.023 | Destabilizing | 0.704 | D | 0.435 | neutral | N | 0.454183451 | None | None | N |
| M/K | 0.496 | ambiguous | 0.5232 | ambiguous | -0.923 | Destabilizing | 0.986 | D | 0.483 | neutral | D | 0.65630756 | None | None | N |
| M/L | 0.2163 | likely_benign | 0.2627 | benign | -1.023 | Destabilizing | 0.31 | N | 0.314 | neutral | N | 0.506390802 | None | None | N |
| M/N | 0.8247 | likely_pathogenic | 0.8493 | pathogenic | -0.957 | Destabilizing | 0.997 | D | 0.556 | neutral | None | None | None | None | N |
| M/P | 0.9502 | likely_pathogenic | 0.9712 | pathogenic | -1.353 | Destabilizing | 0.997 | D | 0.569 | neutral | None | None | None | None | N |
| M/Q | 0.5134 | ambiguous | 0.5119 | ambiguous | -0.891 | Destabilizing | 0.997 | D | 0.48 | neutral | None | None | None | None | N |
| M/R | 0.5537 | ambiguous | 0.5845 | pathogenic | -0.582 | Destabilizing | 0.996 | D | 0.529 | neutral | D | 0.593960116 | None | None | N |
| M/S | 0.8136 | likely_pathogenic | 0.8396 | pathogenic | -1.611 | Destabilizing | 0.969 | D | 0.458 | neutral | None | None | None | None | N |
| M/T | 0.5773 | likely_pathogenic | 0.6503 | pathogenic | -1.379 | Destabilizing | 0.92 | D | 0.445 | neutral | N | 0.512119051 | None | None | N |
| M/V | 0.1839 | likely_benign | 0.2303 | benign | -1.353 | Destabilizing | 0.061 | N | 0.149 | neutral | N | 0.483892158 | None | None | N |
| M/W | 0.8512 | likely_pathogenic | 0.8451 | pathogenic | -0.823 | Destabilizing | 0.999 | D | 0.518 | neutral | None | None | None | None | N |
| M/Y | 0.8185 | likely_pathogenic | 0.8149 | pathogenic | -0.872 | Destabilizing | 0.997 | D | 0.517 | 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.