Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21214 | 63865;63866;63867 | chr2:178587669;178587668;178587667 | chr2:179452396;179452395;179452394 |
| N2AB | 19573 | 58942;58943;58944 | chr2:178587669;178587668;178587667 | chr2:179452396;179452395;179452394 |
| N2A | 18646 | 56161;56162;56163 | chr2:178587669;178587668;178587667 | chr2:179452396;179452395;179452394 |
| N2B | 12149 | 36670;36671;36672 | chr2:178587669;178587668;178587667 | chr2:179452396;179452395;179452394 |
| Novex-1 | 12274 | 37045;37046;37047 | chr2:178587669;178587668;178587667 | chr2:179452396;179452395;179452394 |
| Novex-2 | 12341 | 37246;37247;37248 | chr2:178587669;178587668;178587667 | chr2:179452396;179452395;179452394 |
| 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/A | rs779686062  |
-0.074 | 1.0 | N | 0.733 | 0.545 | 0.486282253068 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| D/A | rs779686062 |
-0.074 | 1.0 | N | 0.733 | 0.545 | 0.486282253068 | gnomAD-4.0.0 | 1.2322E-05 | None | None | None | None | I | None | 2.99168E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.25959E-05 | 0 | 4.97298E-05 |
| D/G | None | None | 1.0 | D | 0.714 | 0.539 | 0.413891365518 | gnomAD-4.0.0 | 6.84554E-07 | None | None | None | None | I | None | 2.99168E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs746677565 |
0.217 | 1.0 | N | 0.638 | 0.411 | 0.374255764437 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 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 | 0.4021 | ambiguous | 0.3837 | ambiguous | 0.1 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.520071604 | None | None | I |
| D/C | 0.8748 | likely_pathogenic | 0.874 | pathogenic | 0.051 | Stabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| D/E | 0.2561 | likely_benign | 0.2448 | benign | -0.281 | Destabilizing | 1.0 | D | 0.463 | neutral | N | 0.440031953 | None | None | I |
| D/F | 0.9027 | likely_pathogenic | 0.9037 | pathogenic | -0.045 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| D/G | 0.367 | ambiguous | 0.3351 | benign | -0.01 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | D | 0.522901266 | None | None | I |
| D/H | 0.5872 | likely_pathogenic | 0.5609 | ambiguous | 0.437 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | D | 0.531078032 | None | None | I |
| D/I | 0.7713 | likely_pathogenic | 0.7768 | pathogenic | 0.317 | Stabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | I |
| D/K | 0.7111 | likely_pathogenic | 0.6852 | pathogenic | 0.568 | Stabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | I |
| D/L | 0.7238 | likely_pathogenic | 0.7191 | pathogenic | 0.317 | Stabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | I |
| D/M | 0.8907 | likely_pathogenic | 0.8965 | pathogenic | 0.178 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| D/N | 0.2208 | likely_benign | 0.2109 | benign | 0.375 | Stabilizing | 1.0 | D | 0.638 | neutral | N | 0.505411583 | None | None | I |
| D/P | 0.7205 | likely_pathogenic | 0.691 | pathogenic | 0.264 | Stabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| D/Q | 0.5759 | likely_pathogenic | 0.5672 | pathogenic | 0.366 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| D/R | 0.7103 | likely_pathogenic | 0.6913 | pathogenic | 0.705 | Stabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| D/S | 0.2557 | likely_benign | 0.2419 | benign | 0.292 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| D/T | 0.4825 | ambiguous | 0.4793 | ambiguous | 0.38 | Stabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| D/V | 0.5789 | likely_pathogenic | 0.5783 | pathogenic | 0.264 | Stabilizing | 1.0 | D | 0.765 | deleterious | N | 0.502179277 | None | None | I |
| D/W | 0.9634 | likely_pathogenic | 0.9636 | pathogenic | -0.027 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/Y | 0.5927 | likely_pathogenic | 0.582 | pathogenic | 0.181 | Stabilizing | 1.0 | D | 0.734 | prob.delet. | N | 0.502484046 | 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.