Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15281 | 46066;46067;46068 | chr2:178620769;178620768;178620767 | chr2:179485496;179485495;179485494 |
| N2AB | 13640 | 41143;41144;41145 | chr2:178620769;178620768;178620767 | chr2:179485496;179485495;179485494 |
| N2A | 12713 | 38362;38363;38364 | chr2:178620769;178620768;178620767 | chr2:179485496;179485495;179485494 |
| N2B | 6216 | 18871;18872;18873 | chr2:178620769;178620768;178620767 | chr2:179485496;179485495;179485494 |
| Novex-1 | 6341 | 19246;19247;19248 | chr2:178620769;178620768;178620767 | chr2:179485496;179485495;179485494 |
| Novex-2 | 6408 | 19447;19448;19449 | chr2:178620769;178620768;178620767 | chr2:179485496;179485495;179485494 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs574423141  |
-1.627 | 0.999 | D | 0.828 | 0.433 | 0.668234073123 | gnomAD-2.1.1 | 7.26E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 5.23081E-04 | None | 0 | 1.79E-05 | 0 |
| L/F | rs574423141 |
-1.627 | 0.999 | D | 0.828 | 0.433 | 0.668234073123 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 6.21118E-04 | 0 |
| L/F | rs574423141 |
-1.627 | 0.999 | D | 0.828 | 0.433 | 0.668234073123 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| L/F | rs574423141 |
-1.627 | 0.999 | D | 0.828 | 0.433 | 0.668234073123 | gnomAD-4.0.0 | 2.23216E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.2404E-06 | 3.29533E-04 | 1.6021E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9156 | likely_pathogenic | 0.8771 | pathogenic | -2.637 | Highly Destabilizing | 0.997 | D | 0.673 | neutral | None | None | None | None | N |
| L/C | 0.9263 | likely_pathogenic | 0.8964 | pathogenic | -2.138 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| L/D | 0.9995 | likely_pathogenic | 0.9992 | pathogenic | -2.683 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| L/E | 0.9966 | likely_pathogenic | 0.9953 | pathogenic | -2.478 | Highly Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| L/F | 0.5135 | ambiguous | 0.5038 | ambiguous | -1.646 | Destabilizing | 0.999 | D | 0.828 | deleterious | D | 0.573257311 | None | None | N |
| L/G | 0.9913 | likely_pathogenic | 0.9869 | pathogenic | -3.185 | Highly Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| L/H | 0.9908 | likely_pathogenic | 0.9866 | pathogenic | -2.54 | Highly Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| L/I | 0.1779 | likely_benign | 0.1688 | benign | -1.066 | Destabilizing | 0.994 | D | 0.581 | neutral | None | None | None | None | N |
| L/K | 0.9939 | likely_pathogenic | 0.9916 | pathogenic | -2.053 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| L/M | 0.3557 | ambiguous | 0.3257 | benign | -1.061 | Destabilizing | 0.999 | D | 0.785 | deleterious | N | 0.509237744 | None | None | N |
| L/N | 0.9972 | likely_pathogenic | 0.9955 | pathogenic | -2.324 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| L/P | 0.9969 | likely_pathogenic | 0.9957 | pathogenic | -1.568 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| L/Q | 0.9858 | likely_pathogenic | 0.9803 | pathogenic | -2.224 | Highly Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| L/R | 0.9856 | likely_pathogenic | 0.9812 | pathogenic | -1.699 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| L/S | 0.9911 | likely_pathogenic | 0.9848 | pathogenic | -3.099 | Highly Destabilizing | 0.999 | D | 0.801 | deleterious | D | 0.572233192 | None | None | N |
| L/T | 0.9668 | likely_pathogenic | 0.9412 | pathogenic | -2.739 | Highly Destabilizing | 0.999 | D | 0.79 | deleterious | None | None | None | None | N |
| L/V | 0.2146 | likely_benign | 0.1921 | benign | -1.568 | Destabilizing | 0.767 | D | 0.392 | neutral | N | 0.469433686 | None | None | N |
| L/W | 0.9674 | likely_pathogenic | 0.9571 | pathogenic | -1.957 | Destabilizing | 1.0 | D | 0.809 | deleterious | D | 0.532847594 | None | None | N |
| L/Y | 0.9726 | likely_pathogenic | 0.9635 | pathogenic | -1.701 | Destabilizing | 1.0 | D | 0.835 | deleterious | 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.