Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1734 | 5425;5426;5427 | chr2:178776664;178776663;178776662 | chr2:179641391;179641390;179641389 |
| N2AB | 1734 | 5425;5426;5427 | chr2:178776664;178776663;178776662 | chr2:179641391;179641390;179641389 |
| N2A | 1734 | 5425;5426;5427 | chr2:178776664;178776663;178776662 | chr2:179641391;179641390;179641389 |
| N2B | 1688 | 5287;5288;5289 | chr2:178776664;178776663;178776662 | chr2:179641391;179641390;179641389 |
| Novex-1 | 1688 | 5287;5288;5289 | chr2:178776664;178776663;178776662 | chr2:179641391;179641390;179641389 |
| Novex-2 | 1688 | 5287;5288;5289 | chr2:178776664;178776663;178776662 | chr2:179641391;179641390;179641389 |
| Novex-3 | 1734 | 5425;5426;5427 | chr2:178776664;178776663;178776662 | chr2:179641391;179641390;179641389 |
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/T | rs1379908886  |
-0.708 | 0.994 | D | 0.699 | 0.603 | 0.852533650957 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| M/T | rs1379908886 |
-0.708 | 0.994 | D | 0.699 | 0.603 | 0.852533650957 | gnomAD-4.0.0 | 7.52501E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.89219E-06 | 0 | 0 |
| M/V | None | None | 0.985 | N | 0.543 | 0.411 | 0.578877614382 | gnomAD-4.0.0 | 1.36818E-06 | None | None | None | None | I | None | 0 | 2.23664E-05 | None | 0 | 0 | None | 0 | 0 | 8.9929E-07 | 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 | 0.9529 | likely_pathogenic | 0.9532 | pathogenic | -1.864 | Destabilizing | 0.989 | D | 0.621 | neutral | None | None | None | None | I |
| M/C | 0.9722 | likely_pathogenic | 0.9696 | pathogenic | -1.638 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| M/D | 0.9989 | likely_pathogenic | 0.9988 | pathogenic | -1.496 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | I |
| M/E | 0.9928 | likely_pathogenic | 0.9917 | pathogenic | -1.441 | Destabilizing | 0.999 | D | 0.708 | prob.delet. | None | None | None | None | I |
| M/F | 0.9377 | likely_pathogenic | 0.9328 | pathogenic | -0.947 | Destabilizing | 0.999 | D | 0.654 | neutral | None | None | None | None | I |
| M/G | 0.9927 | likely_pathogenic | 0.9927 | pathogenic | -2.195 | Highly Destabilizing | 0.995 | D | 0.725 | prob.delet. | None | None | None | None | I |
| M/H | 0.9943 | likely_pathogenic | 0.994 | pathogenic | -1.532 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| M/I | 0.9552 | likely_pathogenic | 0.9533 | pathogenic | -0.988 | Destabilizing | 0.985 | D | 0.599 | neutral | N | 0.50799316 | None | None | I |
| M/K | 0.9879 | likely_pathogenic | 0.9869 | pathogenic | -0.872 | Destabilizing | 0.994 | D | 0.705 | prob.neutral | D | 0.613649203 | None | None | I |
| M/L | 0.6563 | likely_pathogenic | 0.6366 | pathogenic | -0.988 | Destabilizing | 0.927 | D | 0.381 | neutral | N | 0.445162149 | None | None | I |
| M/N | 0.9895 | likely_pathogenic | 0.9887 | pathogenic | -0.832 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | I |
| M/P | 0.9931 | likely_pathogenic | 0.9945 | pathogenic | -1.256 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | I |
| M/Q | 0.9581 | likely_pathogenic | 0.954 | pathogenic | -0.903 | Destabilizing | 0.999 | D | 0.664 | neutral | None | None | None | None | I |
| M/R | 0.9884 | likely_pathogenic | 0.987 | pathogenic | -0.533 | Destabilizing | 0.998 | D | 0.727 | prob.delet. | D | 0.655131564 | None | None | I |
| M/S | 0.9725 | likely_pathogenic | 0.9716 | pathogenic | -1.363 | Destabilizing | 0.995 | D | 0.663 | neutral | None | None | None | None | I |
| M/T | 0.9446 | likely_pathogenic | 0.9374 | pathogenic | -1.204 | Destabilizing | 0.994 | D | 0.699 | prob.neutral | D | 0.572169159 | None | None | I |
| M/V | 0.4967 | ambiguous | 0.4877 | ambiguous | -1.256 | Destabilizing | 0.985 | D | 0.543 | neutral | N | 0.507180132 | None | None | I |
| M/W | 0.9947 | likely_pathogenic | 0.9942 | pathogenic | -1.011 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| M/Y | 0.9919 | likely_pathogenic | 0.9909 | pathogenic | -0.969 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | 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.