Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34988 | 105187;105188;105189 | chr2:178531653;178531652;178531651 | chr2:179396380;179396379;179396378 |
| N2AB | 33347 | 100264;100265;100266 | chr2:178531653;178531652;178531651 | chr2:179396380;179396379;179396378 |
| N2A | 32420 | 97483;97484;97485 | chr2:178531653;178531652;178531651 | chr2:179396380;179396379;179396378 |
| N2B | 25923 | 77992;77993;77994 | chr2:178531653;178531652;178531651 | chr2:179396380;179396379;179396378 |
| Novex-1 | 26048 | 78367;78368;78369 | chr2:178531653;178531652;178531651 | chr2:179396380;179396379;179396378 |
| Novex-2 | 26115 | 78568;78569;78570 | chr2:178531653;178531652;178531651 | chr2:179396380;179396379;179396378 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs1420224634  |
-0.94 | 0.675 | N | 0.326 | 0.191 | 0.580864329964 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| I/L | rs1420224634 |
-0.94 | 0.675 | N | 0.326 | 0.191 | 0.580864329964 | gnomAD-4.0.0 | 6.84143E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51889E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/N | None | None | 0.988 | N | 0.589 | 0.511 | 0.818383550975 | gnomAD-4.0.0 | 4.77271E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 8.31716E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | None | None | 0.675 | N | 0.336 | 0.168 | 0.567643136482 | gnomAD-4.0.0 | 2.05243E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69821E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9363 | likely_pathogenic | 0.9475 | pathogenic | -2.544 | Highly Destabilizing | 0.863 | D | 0.453 | neutral | None | None | None | None | N |
| I/C | 0.9344 | likely_pathogenic | 0.9473 | pathogenic | -1.837 | Destabilizing | 0.999 | D | 0.519 | neutral | None | None | None | None | N |
| I/D | 0.9929 | likely_pathogenic | 0.994 | pathogenic | -2.482 | Highly Destabilizing | 0.991 | D | 0.59 | neutral | None | None | None | None | N |
| I/E | 0.9792 | likely_pathogenic | 0.9814 | pathogenic | -2.285 | Highly Destabilizing | 0.939 | D | 0.565 | neutral | None | None | None | None | N |
| I/F | 0.2234 | likely_benign | 0.2484 | benign | -1.525 | Destabilizing | 0.852 | D | 0.487 | neutral | N | 0.434530133 | None | None | N |
| I/G | 0.9848 | likely_pathogenic | 0.9874 | pathogenic | -3.08 | Highly Destabilizing | 0.969 | D | 0.574 | neutral | None | None | None | None | N |
| I/H | 0.9222 | likely_pathogenic | 0.9308 | pathogenic | -2.445 | Highly Destabilizing | 0.982 | D | 0.599 | neutral | None | None | None | None | N |
| I/K | 0.9449 | likely_pathogenic | 0.9472 | pathogenic | -2.021 | Highly Destabilizing | 0.079 | N | 0.4 | neutral | None | None | None | None | N |
| I/L | 0.2694 | likely_benign | 0.3027 | benign | -1.013 | Destabilizing | 0.675 | D | 0.326 | neutral | N | 0.511662765 | None | None | N |
| I/M | 0.2568 | likely_benign | 0.2813 | benign | -0.904 | Destabilizing | 0.996 | D | 0.55 | neutral | N | 0.487733926 | None | None | N |
| I/N | 0.8841 | likely_pathogenic | 0.895 | pathogenic | -2.225 | Highly Destabilizing | 0.988 | D | 0.589 | neutral | N | 0.488747884 | None | None | N |
| I/P | 0.9954 | likely_pathogenic | 0.9961 | pathogenic | -1.501 | Destabilizing | 0.997 | D | 0.583 | neutral | None | None | None | None | N |
| I/Q | 0.9452 | likely_pathogenic | 0.9533 | pathogenic | -2.127 | Highly Destabilizing | 0.982 | D | 0.59 | neutral | None | None | None | None | N |
| I/R | 0.9004 | likely_pathogenic | 0.9072 | pathogenic | -1.664 | Destabilizing | 0.884 | D | 0.573 | neutral | None | None | None | None | N |
| I/S | 0.9254 | likely_pathogenic | 0.9365 | pathogenic | -2.979 | Highly Destabilizing | 0.92 | D | 0.52 | neutral | D | 0.532328825 | None | None | N |
| I/T | 0.8363 | likely_pathogenic | 0.8614 | pathogenic | -2.633 | Highly Destabilizing | 0.959 | D | 0.501 | neutral | D | 0.524440061 | None | None | N |
| I/V | 0.193 | likely_benign | 0.1953 | benign | -1.501 | Destabilizing | 0.675 | D | 0.336 | neutral | N | 0.47379781 | None | None | N |
| I/W | 0.9052 | likely_pathogenic | 0.9201 | pathogenic | -1.851 | Destabilizing | 0.998 | D | 0.569 | neutral | None | None | None | None | N |
| I/Y | 0.6067 | likely_pathogenic | 0.6464 | pathogenic | -1.588 | Destabilizing | 0.079 | N | 0.236 | 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.