Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21508 | 64747;64748;64749 | chr2:178585222;178585221;178585220 | chr2:179449949;179449948;179449947 |
| N2AB | 19867 | 59824;59825;59826 | chr2:178585222;178585221;178585220 | chr2:179449949;179449948;179449947 |
| N2A | 18940 | 57043;57044;57045 | chr2:178585222;178585221;178585220 | chr2:179449949;179449948;179449947 |
| N2B | 12443 | 37552;37553;37554 | chr2:178585222;178585221;178585220 | chr2:179449949;179449948;179449947 |
| Novex-1 | 12568 | 37927;37928;37929 | chr2:178585222;178585221;178585220 | chr2:179449949;179449948;179449947 |
| Novex-2 | 12635 | 38128;38129;38130 | chr2:178585222;178585221;178585220 | chr2:179449949;179449948;179449947 |
| 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/F | None | None | 0.317 | N | 0.373 | 0.127 | 0.721282347704 | gnomAD-4.0.0 | 2.73761E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59888E-06 | 0 | 0 |
| V/I | rs759982511  |
-0.108 | None | N | 0.225 | 0.115 | 0.460703734027 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.30745E-04 | None | 0 | 0 | 0 |
| V/I | rs759982511 |
-0.108 | None | N | 0.225 | 0.115 | 0.460703734027 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs759982511 |
-0.108 | None | N | 0.225 | 0.115 | 0.460703734027 | gnomAD-4.0.0 | 3.90521E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.57839E-05 | 7.68791E-05 | 3.20328E-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 | 0.1273 | likely_benign | 0.1236 | benign | -0.348 | Destabilizing | None | N | 0.142 | neutral | N | 0.496269238 | None | None | I |
| V/C | 0.5703 | likely_pathogenic | 0.5446 | ambiguous | -0.833 | Destabilizing | 0.824 | D | 0.367 | neutral | None | None | None | None | I |
| V/D | 0.2467 | likely_benign | 0.2197 | benign | -0.128 | Destabilizing | 0.484 | N | 0.382 | neutral | N | 0.478723627 | None | None | I |
| V/E | 0.1908 | likely_benign | 0.1683 | benign | -0.233 | Destabilizing | 0.38 | N | 0.363 | neutral | None | None | None | None | I |
| V/F | 0.1101 | likely_benign | 0.1221 | benign | -0.627 | Destabilizing | 0.317 | N | 0.373 | neutral | N | 0.503293998 | None | None | I |
| V/G | 0.1597 | likely_benign | 0.1511 | benign | -0.429 | Destabilizing | 0.062 | N | 0.418 | neutral | N | 0.511124047 | None | None | I |
| V/H | 0.3379 | likely_benign | 0.3203 | benign | -0.026 | Destabilizing | 0.935 | D | 0.372 | neutral | None | None | None | None | I |
| V/I | 0.0663 | likely_benign | 0.0708 | benign | -0.277 | Destabilizing | None | N | 0.225 | neutral | N | 0.513721635 | None | None | I |
| V/K | 0.1957 | likely_benign | 0.1584 | benign | -0.389 | Destabilizing | 0.149 | N | 0.392 | neutral | None | None | None | None | I |
| V/L | 0.1044 | likely_benign | 0.1039 | benign | -0.277 | Destabilizing | None | N | 0.127 | neutral | N | 0.490114057 | None | None | I |
| V/M | 0.0959 | likely_benign | 0.0989 | benign | -0.532 | Destabilizing | 0.007 | N | 0.199 | neutral | None | None | None | None | I |
| V/N | 0.1568 | likely_benign | 0.1509 | benign | -0.245 | Destabilizing | 0.555 | D | 0.384 | neutral | None | None | None | None | I |
| V/P | 0.3218 | likely_benign | 0.3289 | benign | -0.272 | Destabilizing | 0.555 | D | 0.373 | neutral | None | None | None | None | I |
| V/Q | 0.1888 | likely_benign | 0.1651 | benign | -0.412 | Destabilizing | 0.555 | D | 0.373 | neutral | None | None | None | None | I |
| V/R | 0.2027 | likely_benign | 0.1608 | benign | 0.017 | Stabilizing | 0.555 | D | 0.383 | neutral | None | None | None | None | I |
| V/S | 0.1351 | likely_benign | 0.1301 | benign | -0.591 | Destabilizing | 0.081 | N | 0.391 | neutral | None | None | None | None | I |
| V/T | 0.1272 | likely_benign | 0.1244 | benign | -0.596 | Destabilizing | 0.149 | N | 0.327 | neutral | None | None | None | None | I |
| V/W | 0.6199 | likely_pathogenic | 0.6181 | pathogenic | -0.701 | Destabilizing | 0.935 | D | 0.396 | neutral | None | None | None | None | I |
| V/Y | 0.3349 | likely_benign | 0.3316 | benign | -0.426 | Destabilizing | 0.555 | D | 0.373 | neutral | None | None | 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.