Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1900 | 5923;5924;5925 | chr2:178776166;178776165;178776164 | chr2:179640893;179640892;179640891 |
| N2AB | 1900 | 5923;5924;5925 | chr2:178776166;178776165;178776164 | chr2:179640893;179640892;179640891 |
| N2A | 1900 | 5923;5924;5925 | chr2:178776166;178776165;178776164 | chr2:179640893;179640892;179640891 |
| N2B | 1854 | 5785;5786;5787 | chr2:178776166;178776165;178776164 | chr2:179640893;179640892;179640891 |
| Novex-1 | 1854 | 5785;5786;5787 | chr2:178776166;178776165;178776164 | chr2:179640893;179640892;179640891 |
| Novex-2 | 1854 | 5785;5786;5787 | chr2:178776166;178776165;178776164 | chr2:179640893;179640892;179640891 |
| Novex-3 | 1900 | 5923;5924;5925 | chr2:178776166;178776165;178776164 | chr2:179640893;179640892;179640891 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | rs878931921  |
None | 0.961 | N | 0.553 | 0.502 | None | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | None | None | 0.963 | N | 0.457 | 0.221 | 0.455909487837 | gnomAD-4.0.0 | 1.02611E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.25902E-05 | 0 | 1.65579E-05 |
| V/M | rs750823043 |
-1.183 | 1.0 | N | 0.475 | 0.274 | None | gnomAD-2.1.1 | 2.48E-05 | None | None | None | None | N | None | 4.01E-05 | 0 | None | 0 | 1.00261E-04 | None | 3.27E-05 | None | 0 | 2.33E-05 | 0 |
| V/M | rs750823043 |
-1.183 | 1.0 | N | 0.475 | 0.274 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.06954E-04 | 4.77555E-04 |
| V/M | rs750823043 |
-1.183 | 1.0 | N | 0.475 | 0.274 | None | gnomAD-4.0.0 | 2.47831E-05 | None | None | None | None | N | None | 1.06795E-04 | 0 | None | 3.37769E-05 | 6.683E-05 | None | 0 | 1.64366E-04 | 1.01695E-05 | 8.78252E-05 | 1.12022E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.407 | ambiguous | 0.3828 | ambiguous | -1.756 | Destabilizing | 0.248 | N | 0.201 | neutral | N | 0.469261396 | None | None | N |
| V/C | 0.9088 | likely_pathogenic | 0.9111 | pathogenic | -1.433 | Destabilizing | 1.0 | D | 0.555 | neutral | None | None | None | None | N |
| V/D | 0.898 | likely_pathogenic | 0.8778 | pathogenic | -2.014 | Highly Destabilizing | 0.996 | D | 0.654 | neutral | None | None | None | None | N |
| V/E | 0.7617 | likely_pathogenic | 0.7472 | pathogenic | -1.995 | Destabilizing | 0.994 | D | 0.537 | neutral | N | 0.461818967 | None | None | N |
| V/F | 0.523 | ambiguous | 0.4842 | ambiguous | -1.429 | Destabilizing | 0.999 | D | 0.565 | neutral | None | None | None | None | N |
| V/G | 0.5981 | likely_pathogenic | 0.5849 | pathogenic | -2.1 | Highly Destabilizing | 0.961 | D | 0.553 | neutral | N | 0.504817636 | None | None | N |
| V/H | 0.9039 | likely_pathogenic | 0.9045 | pathogenic | -1.579 | Destabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | N |
| V/I | 0.1117 | likely_benign | 0.1075 | benign | -0.889 | Destabilizing | 0.97 | D | 0.474 | neutral | None | None | None | None | N |
| V/K | 0.8375 | likely_pathogenic | 0.8041 | pathogenic | -1.394 | Destabilizing | 0.991 | D | 0.538 | neutral | None | None | None | None | N |
| V/L | 0.4411 | ambiguous | 0.4205 | ambiguous | -0.889 | Destabilizing | 0.963 | D | 0.457 | neutral | N | 0.459204944 | None | None | N |
| V/M | 0.3527 | ambiguous | 0.3196 | benign | -0.726 | Destabilizing | 1.0 | D | 0.475 | neutral | N | 0.50744401 | None | None | N |
| V/N | 0.6895 | likely_pathogenic | 0.6736 | pathogenic | -1.298 | Destabilizing | 0.996 | D | 0.667 | neutral | None | None | None | None | N |
| V/P | 0.9138 | likely_pathogenic | 0.9344 | pathogenic | -1.145 | Destabilizing | 0.999 | D | 0.618 | neutral | None | None | None | None | N |
| V/Q | 0.6957 | likely_pathogenic | 0.7074 | pathogenic | -1.495 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| V/R | 0.7702 | likely_pathogenic | 0.7497 | pathogenic | -0.851 | Destabilizing | 0.996 | D | 0.667 | neutral | None | None | None | None | N |
| V/S | 0.4777 | ambiguous | 0.4752 | ambiguous | -1.841 | Destabilizing | 0.942 | D | 0.514 | neutral | None | None | None | None | N |
| V/T | 0.2721 | likely_benign | 0.2728 | benign | -1.71 | Destabilizing | 0.304 | N | 0.265 | neutral | None | None | None | None | N |
| V/W | 0.9711 | likely_pathogenic | 0.9713 | pathogenic | -1.628 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| V/Y | 0.9041 | likely_pathogenic | 0.9 | pathogenic | -1.337 | Destabilizing | 0.999 | D | 0.573 | 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.