Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21423 | 64492;64493;64494 | chr2:178586634;178586633;178586632 | chr2:179451361;179451360;179451359 |
| N2AB | 19782 | 59569;59570;59571 | chr2:178586634;178586633;178586632 | chr2:179451361;179451360;179451359 |
| N2A | 18855 | 56788;56789;56790 | chr2:178586634;178586633;178586632 | chr2:179451361;179451360;179451359 |
| N2B | 12358 | 37297;37298;37299 | chr2:178586634;178586633;178586632 | chr2:179451361;179451360;179451359 |
| Novex-1 | 12483 | 37672;37673;37674 | chr2:178586634;178586633;178586632 | chr2:179451361;179451360;179451359 |
| Novex-2 | 12550 | 37873;37874;37875 | chr2:178586634;178586633;178586632 | chr2:179451361;179451360;179451359 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/Y | rs761820626  |
0.603 | 1.0 | N | 0.655 | 0.407 | 0.635861425549 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| D/Y | rs761820626 |
0.603 | 1.0 | N | 0.655 | 0.407 | 0.635861425549 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.94175E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs761820626 |
0.603 | 1.0 | N | 0.655 | 0.407 | 0.635861425549 | gnomAD-4.0.0 | 1.23989E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.23334E-05 | None | 0 | 0 | 8.47877E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3212 | likely_benign | 0.2584 | benign | 0.011 | Stabilizing | 1.0 | D | 0.633 | neutral | N | 0.452160596 | None | None | I |
| D/C | 0.8463 | likely_pathogenic | 0.7744 | pathogenic | -0.222 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | I |
| D/E | 0.2262 | likely_benign | 0.1874 | benign | -0.34 | Destabilizing | 1.0 | D | 0.373 | neutral | N | 0.465628539 | None | None | I |
| D/F | 0.8373 | likely_pathogenic | 0.7837 | pathogenic | 0.413 | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| D/G | 0.2001 | likely_benign | 0.1621 | benign | -0.234 | Destabilizing | 1.0 | D | 0.653 | neutral | N | 0.454200824 | None | None | I |
| D/H | 0.5775 | likely_pathogenic | 0.4764 | ambiguous | 0.859 | Stabilizing | 1.0 | D | 0.628 | neutral | N | 0.511939618 | None | None | I |
| D/I | 0.7224 | likely_pathogenic | 0.6236 | pathogenic | 0.623 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| D/K | 0.7192 | likely_pathogenic | 0.6067 | pathogenic | 0.419 | Stabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | I |
| D/L | 0.6967 | likely_pathogenic | 0.6198 | pathogenic | 0.623 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| D/M | 0.8317 | likely_pathogenic | 0.7727 | pathogenic | 0.404 | Stabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| D/N | 0.1753 | likely_benign | 0.1418 | benign | -0.254 | Destabilizing | 1.0 | D | 0.603 | neutral | N | 0.492428351 | None | None | I |
| D/P | 0.9152 | likely_pathogenic | 0.884 | pathogenic | 0.442 | Stabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | I |
| D/Q | 0.5809 | likely_pathogenic | 0.4882 | ambiguous | -0.142 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | I |
| D/R | 0.7689 | likely_pathogenic | 0.6765 | pathogenic | 0.793 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| D/S | 0.2221 | likely_benign | 0.1739 | benign | -0.328 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | I |
| D/T | 0.4048 | ambiguous | 0.3156 | benign | -0.107 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| D/V | 0.4707 | ambiguous | 0.3788 | ambiguous | 0.442 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.495527371 | None | None | I |
| D/W | 0.9678 | likely_pathogenic | 0.9519 | pathogenic | 0.582 | Stabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| D/Y | 0.484 | ambiguous | 0.3911 | ambiguous | 0.687 | Stabilizing | 1.0 | D | 0.655 | neutral | N | 0.506707157 | 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.