Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26411 | 79456;79457;79458 | chr2:178566901;178566900;178566899 | chr2:179431628;179431627;179431626 |
| N2AB | 24770 | 74533;74534;74535 | chr2:178566901;178566900;178566899 | chr2:179431628;179431627;179431626 |
| N2A | 23843 | 71752;71753;71754 | chr2:178566901;178566900;178566899 | chr2:179431628;179431627;179431626 |
| N2B | 17346 | 52261;52262;52263 | chr2:178566901;178566900;178566899 | chr2:179431628;179431627;179431626 |
| Novex-1 | 17471 | 52636;52637;52638 | chr2:178566901;178566900;178566899 | chr2:179431628;179431627;179431626 |
| Novex-2 | 17538 | 52837;52838;52839 | chr2:178566901;178566900;178566899 | chr2:179431628;179431627;179431626 |
| 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/E | None | None | 0.067 | N | 0.239 | 0.079 | 0.0762999501168 | gnomAD-4.0.0 | 6.84293E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99552E-07 | 0 | 0 |
| D/G | None | None | 0.958 | N | 0.656 | 0.421 | 0.305730143919 | gnomAD-4.0.0 | 6.84292E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99544E-07 | 0 | 0 |
| D/N | rs2154165912  |
None | 0.988 | N | 0.7 | 0.261 | 0.26547132957 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 6.17284E-04 | 1.3125E-06 | 0 | 0 |
| D/V | rs755457407 |
0.447 | 0.994 | N | 0.739 | 0.477 | 0.502691689211 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| D/V | rs755457407 |
0.447 | 0.994 | N | 0.739 | 0.477 | 0.502691689211 | gnomAD-4.0.0 | 6.84292E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99544E-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 | 0.1003 | likely_benign | 0.0989 | benign | 0.055 | Stabilizing | 0.958 | D | 0.612 | neutral | N | 0.404174648 | None | None | I |
| D/C | 0.4839 | ambiguous | 0.5189 | ambiguous | -0.021 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| D/E | 0.0929 | likely_benign | 0.0974 | benign | -0.281 | Destabilizing | 0.067 | N | 0.239 | neutral | N | 0.374563817 | None | None | I |
| D/F | 0.4679 | ambiguous | 0.455 | ambiguous | -0.055 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| D/G | 0.1482 | likely_benign | 0.1479 | benign | -0.059 | Destabilizing | 0.958 | D | 0.656 | neutral | N | 0.441732959 | None | None | I |
| D/H | 0.2432 | likely_benign | 0.2593 | benign | 0.459 | Stabilizing | 0.998 | D | 0.725 | prob.delet. | N | 0.496412806 | None | None | I |
| D/I | 0.188 | likely_benign | 0.1926 | benign | 0.283 | Stabilizing | 0.995 | D | 0.752 | deleterious | None | None | None | None | I |
| D/K | 0.2835 | likely_benign | 0.2955 | benign | 0.506 | Stabilizing | 0.982 | D | 0.673 | neutral | None | None | None | None | I |
| D/L | 0.2212 | likely_benign | 0.2329 | benign | 0.283 | Stabilizing | 0.991 | D | 0.739 | prob.delet. | None | None | None | None | I |
| D/M | 0.3942 | ambiguous | 0.4129 | ambiguous | 0.136 | Stabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| D/N | 0.1 | likely_benign | 0.1011 | benign | 0.293 | Stabilizing | 0.988 | D | 0.7 | prob.neutral | N | 0.483675582 | None | None | I |
| D/P | 0.507 | ambiguous | 0.4538 | ambiguous | 0.226 | Stabilizing | 0.995 | D | 0.728 | prob.delet. | None | None | None | None | I |
| D/Q | 0.2099 | likely_benign | 0.2259 | benign | 0.29 | Stabilizing | 0.982 | D | 0.761 | deleterious | None | None | None | None | I |
| D/R | 0.341 | ambiguous | 0.3497 | ambiguous | 0.679 | Stabilizing | 0.991 | D | 0.731 | prob.delet. | None | None | None | None | I |
| D/S | 0.0908 | likely_benign | 0.0933 | benign | 0.202 | Stabilizing | 0.968 | D | 0.662 | neutral | None | None | None | None | I |
| D/T | 0.1523 | likely_benign | 0.1572 | benign | 0.295 | Stabilizing | 0.991 | D | 0.689 | prob.neutral | None | None | None | None | I |
| D/V | 0.1105 | likely_benign | 0.1113 | benign | 0.226 | Stabilizing | 0.994 | D | 0.739 | prob.delet. | N | 0.446850777 | None | None | I |
| D/W | 0.8374 | likely_pathogenic | 0.8491 | pathogenic | -0.022 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| D/Y | 0.2234 | likely_benign | 0.2306 | benign | 0.171 | Stabilizing | 0.999 | D | 0.743 | deleterious | N | 0.47188899 | 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.