Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21485 | 64678;64679;64680 | chr2:178585291;178585290;178585289 | chr2:179450018;179450017;179450016 |
| N2AB | 19844 | 59755;59756;59757 | chr2:178585291;178585290;178585289 | chr2:179450018;179450017;179450016 |
| N2A | 18917 | 56974;56975;56976 | chr2:178585291;178585290;178585289 | chr2:179450018;179450017;179450016 |
| N2B | 12420 | 37483;37484;37485 | chr2:178585291;178585290;178585289 | chr2:179450018;179450017;179450016 |
| Novex-1 | 12545 | 37858;37859;37860 | chr2:178585291;178585290;178585289 | chr2:179450018;179450017;179450016 |
| Novex-2 | 12612 | 38059;38060;38061 | chr2:178585291;178585290;178585289 | chr2:179450018;179450017;179450016 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs746903647  |
0.025 | 0.999 | N | 0.534 | 0.316 | 0.18274738541 | gnomAD-2.1.1 | 2.43E-05 | None | None | None | None | N | None | 0 | 5.85E-05 | None | 0 | 0 | None | 6.62E-05 | None | 0 | 1.79E-05 | 0 |
| R/Q | rs746903647 |
0.025 | 0.999 | N | 0.534 | 0.316 | 0.18274738541 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 1.94099E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs746903647 |
0.025 | 0.999 | N | 0.534 | 0.316 | 0.18274738541 | gnomAD-4.0.0 | 2.66823E-05 | None | None | None | None | N | None | 2.67723E-05 | 1.67442E-05 | None | 0 | 2.23234E-05 | None | 0 | 0 | 2.46008E-05 | 7.72116E-05 | 4.80923E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7733 | likely_pathogenic | 0.7029 | pathogenic | -0.382 | Destabilizing | 0.863 | D | 0.449 | neutral | None | None | None | None | N |
| R/C | 0.3497 | ambiguous | 0.2933 | benign | -0.521 | Destabilizing | 0.999 | D | 0.491 | neutral | None | None | None | None | N |
| R/D | 0.9281 | likely_pathogenic | 0.8979 | pathogenic | -0.017 | Destabilizing | 0.997 | D | 0.522 | neutral | None | None | None | None | N |
| R/E | 0.7249 | likely_pathogenic | 0.6401 | pathogenic | 0.125 | Stabilizing | 0.99 | D | 0.489 | neutral | None | None | None | None | N |
| R/F | 0.8031 | likely_pathogenic | 0.7402 | pathogenic | -0.167 | Destabilizing | 0.991 | D | 0.519 | neutral | None | None | None | None | N |
| R/G | 0.7736 | likely_pathogenic | 0.697 | pathogenic | -0.69 | Destabilizing | 0.994 | D | 0.52 | neutral | N | 0.474961685 | None | None | N |
| R/H | 0.1911 | likely_benign | 0.156 | benign | -1.057 | Destabilizing | 0.997 | D | 0.566 | neutral | None | None | None | None | N |
| R/I | 0.4689 | ambiguous | 0.3725 | ambiguous | 0.439 | Stabilizing | 0.17 | N | 0.372 | neutral | None | None | None | None | N |
| R/K | 0.2171 | likely_benign | 0.1817 | benign | -0.418 | Destabilizing | 0.975 | D | 0.511 | neutral | None | None | None | None | N |
| R/L | 0.4624 | ambiguous | 0.3854 | ambiguous | 0.439 | Stabilizing | 0.725 | D | 0.412 | neutral | N | 0.501036686 | None | None | N |
| R/M | 0.5406 | ambiguous | 0.4388 | ambiguous | -0.167 | Destabilizing | 0.991 | D | 0.556 | neutral | None | None | None | None | N |
| R/N | 0.8473 | likely_pathogenic | 0.7954 | pathogenic | -0.223 | Destabilizing | 0.997 | D | 0.537 | neutral | None | None | None | None | N |
| R/P | 0.9383 | likely_pathogenic | 0.9175 | pathogenic | 0.187 | Stabilizing | 0.998 | D | 0.525 | neutral | N | 0.486482574 | None | None | N |
| R/Q | 0.2145 | likely_benign | 0.1812 | benign | -0.225 | Destabilizing | 0.999 | D | 0.534 | neutral | N | 0.490494406 | None | None | N |
| R/S | 0.8388 | likely_pathogenic | 0.7757 | pathogenic | -0.773 | Destabilizing | 0.969 | D | 0.509 | neutral | None | None | None | None | N |
| R/T | 0.5595 | ambiguous | 0.4462 | ambiguous | -0.445 | Destabilizing | 0.939 | D | 0.527 | neutral | None | None | None | None | N |
| R/V | 0.5529 | ambiguous | 0.4812 | ambiguous | 0.187 | Stabilizing | 0.079 | N | 0.375 | neutral | None | None | None | None | N |
| R/W | 0.3482 | ambiguous | 0.2735 | benign | 0.016 | Stabilizing | 0.999 | D | 0.498 | neutral | None | None | None | None | N |
| R/Y | 0.6355 | likely_pathogenic | 0.5439 | ambiguous | 0.335 | Stabilizing | 0.997 | D | 0.532 | 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.