Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31548 | 94867;94868;94869 | chr2:178546786;178546785;178546784 | chr2:179411513;179411512;179411511 |
| N2AB | 29907 | 89944;89945;89946 | chr2:178546786;178546785;178546784 | chr2:179411513;179411512;179411511 |
| N2A | 28980 | 87163;87164;87165 | chr2:178546786;178546785;178546784 | chr2:179411513;179411512;179411511 |
| N2B | 22483 | 67672;67673;67674 | chr2:178546786;178546785;178546784 | chr2:179411513;179411512;179411511 |
| Novex-1 | 22608 | 68047;68048;68049 | chr2:178546786;178546785;178546784 | chr2:179411513;179411512;179411511 |
| Novex-2 | 22675 | 68248;68249;68250 | chr2:178546786;178546785;178546784 | chr2:179411513;179411512;179411511 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs1697361370  |
None | 0.101 | N | 0.343 | 0.035 | 0.322230723748 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs1697361370 |
None | 0.101 | N | 0.343 | 0.035 | 0.322230723748 | gnomAD-4.0.0 | 3.09865E-06 | None | None | None | None | N | None | 0 | 1.66717E-05 | None | 0 | 0 | None | 0 | 0 | 2.54295E-06 | 0 | 1.60108E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1422 | likely_benign | 0.1285 | benign | -1.147 | Destabilizing | 0.047 | N | 0.221 | neutral | N | 0.441212884 | None | None | N |
| V/C | 0.5379 | ambiguous | 0.4995 | ambiguous | -0.755 | Destabilizing | 0.94 | D | 0.471 | neutral | None | None | None | None | N |
| V/D | 0.3162 | likely_benign | 0.2951 | benign | -0.758 | Destabilizing | 0.351 | N | 0.518 | neutral | N | 0.445061265 | None | None | N |
| V/E | 0.29 | likely_benign | 0.268 | benign | -0.81 | Destabilizing | 0.418 | N | 0.462 | neutral | None | None | None | None | N |
| V/F | 0.1079 | likely_benign | 0.1009 | benign | -0.997 | Destabilizing | 0.001 | N | 0.151 | neutral | N | 0.469516993 | None | None | N |
| V/G | 0.1593 | likely_benign | 0.1496 | benign | -1.397 | Destabilizing | 0.183 | N | 0.49 | neutral | N | 0.498626392 | None | None | N |
| V/H | 0.4423 | ambiguous | 0.3934 | ambiguous | -0.936 | Destabilizing | 0.002 | N | 0.351 | neutral | None | None | None | None | N |
| V/I | 0.0766 | likely_benign | 0.0737 | benign | -0.593 | Destabilizing | 0.101 | N | 0.343 | neutral | N | 0.468650201 | None | None | N |
| V/K | 0.3731 | ambiguous | 0.3236 | benign | -0.945 | Destabilizing | 0.418 | N | 0.456 | neutral | None | None | None | None | N |
| V/L | 0.1344 | likely_benign | 0.1206 | benign | -0.593 | Destabilizing | 0.047 | N | 0.241 | neutral | N | 0.445061265 | None | None | N |
| V/M | 0.1385 | likely_benign | 0.1275 | benign | -0.451 | Destabilizing | 0.836 | D | 0.437 | neutral | None | None | None | None | N |
| V/N | 0.2144 | likely_benign | 0.1957 | benign | -0.651 | Destabilizing | 0.418 | N | 0.517 | neutral | None | None | None | None | N |
| V/P | 0.462 | ambiguous | 0.4129 | ambiguous | -0.741 | Destabilizing | 0.593 | D | 0.513 | neutral | None | None | None | None | N |
| V/Q | 0.2947 | likely_benign | 0.2613 | benign | -0.866 | Destabilizing | 0.593 | D | 0.498 | neutral | None | None | None | None | N |
| V/R | 0.3029 | likely_benign | 0.2651 | benign | -0.406 | Destabilizing | 0.593 | D | 0.529 | neutral | None | None | None | None | N |
| V/S | 0.1652 | likely_benign | 0.1521 | benign | -1.128 | Destabilizing | 0.012 | N | 0.257 | neutral | None | None | None | None | N |
| V/T | 0.171 | likely_benign | 0.1563 | benign | -1.076 | Destabilizing | 0.129 | N | 0.282 | neutral | None | None | None | None | N |
| V/W | 0.6514 | likely_pathogenic | 0.5947 | pathogenic | -1.121 | Destabilizing | 0.836 | D | 0.562 | neutral | None | None | None | None | N |
| V/Y | 0.3335 | likely_benign | 0.2933 | benign | -0.844 | Destabilizing | None | N | 0.153 | 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.