Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31047 | 93364;93365;93366 | chr2:178548487;178548486;178548485 | chr2:179413214;179413213;179413212 |
| N2AB | 29406 | 88441;88442;88443 | chr2:178548487;178548486;178548485 | chr2:179413214;179413213;179413212 |
| N2A | 28479 | 85660;85661;85662 | chr2:178548487;178548486;178548485 | chr2:179413214;179413213;179413212 |
| N2B | 21982 | 66169;66170;66171 | chr2:178548487;178548486;178548485 | chr2:179413214;179413213;179413212 |
| Novex-1 | 22107 | 66544;66545;66546 | chr2:178548487;178548486;178548485 | chr2:179413214;179413213;179413212 |
| Novex-2 | 22174 | 66745;66746;66747 | chr2:178548487;178548486;178548485 | chr2:179413214;179413213;179413212 |
| 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 | rs753897943  |
0.6 | 1.0 | N | 0.69 | 0.341 | 0.1749357433 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 8.91E-06 | 0 |
| R/Q | rs753897943 |
0.6 | 1.0 | N | 0.69 | 0.341 | 0.1749357433 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs753897943 |
0.6 | 1.0 | N | 0.69 | 0.341 | 0.1749357433 | gnomAD-4.0.0 | 1.11544E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01711E-05 | 5.48932E-05 | 1.60113E-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 | 0.607 | likely_pathogenic | 0.5968 | pathogenic | 0.257 | Stabilizing | 0.999 | D | 0.588 | neutral | None | None | None | None | I |
| R/C | 0.3247 | likely_benign | 0.341 | ambiguous | 0.156 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | I |
| R/D | 0.871 | likely_pathogenic | 0.8668 | pathogenic | -0.175 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| R/E | 0.6859 | likely_pathogenic | 0.6709 | pathogenic | -0.104 | Destabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | I |
| R/F | 0.8048 | likely_pathogenic | 0.7971 | pathogenic | 0.077 | Stabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| R/G | 0.531 | ambiguous | 0.5204 | ambiguous | 0.062 | Stabilizing | 1.0 | D | 0.603 | neutral | N | 0.474093306 | None | None | I |
| R/H | 0.183 | likely_benign | 0.1838 | benign | -0.614 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| R/I | 0.5653 | likely_pathogenic | 0.5186 | ambiguous | 0.733 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| R/K | 0.1795 | likely_benign | 0.1743 | benign | 0.215 | Stabilizing | 0.998 | D | 0.478 | neutral | None | None | None | None | I |
| R/L | 0.4832 | ambiguous | 0.4561 | ambiguous | 0.733 | Stabilizing | 1.0 | D | 0.603 | neutral | N | 0.480365918 | None | None | I |
| R/M | 0.5767 | likely_pathogenic | 0.5498 | ambiguous | 0.151 | Stabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| R/N | 0.8024 | likely_pathogenic | 0.801 | pathogenic | 0.388 | Stabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | I |
| R/P | 0.5308 | ambiguous | 0.5202 | ambiguous | 0.595 | Stabilizing | 1.0 | D | 0.669 | neutral | N | 0.332445049 | None | None | I |
| R/Q | 0.199 | likely_benign | 0.1996 | benign | 0.356 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | N | 0.479499126 | None | None | I |
| R/S | 0.7567 | likely_pathogenic | 0.7561 | pathogenic | 0.225 | Stabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | I |
| R/T | 0.5902 | likely_pathogenic | 0.5662 | pathogenic | 0.422 | Stabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | I |
| R/V | 0.5924 | likely_pathogenic | 0.5664 | pathogenic | 0.595 | Stabilizing | 1.0 | D | 0.658 | neutral | None | None | None | None | I |
| R/W | 0.3722 | ambiguous | 0.3561 | ambiguous | -0.078 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| R/Y | 0.6243 | likely_pathogenic | 0.6282 | pathogenic | 0.335 | Stabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | I |
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.