Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22300 | 67123;67124;67125 | chr2:178580481;178580480;178580479 | chr2:179445208;179445207;179445206 |
| N2AB | 20659 | 62200;62201;62202 | chr2:178580481;178580480;178580479 | chr2:179445208;179445207;179445206 |
| N2A | 19732 | 59419;59420;59421 | chr2:178580481;178580480;178580479 | chr2:179445208;179445207;179445206 |
| N2B | 13235 | 39928;39929;39930 | chr2:178580481;178580480;178580479 | chr2:179445208;179445207;179445206 |
| Novex-1 | 13360 | 40303;40304;40305 | chr2:178580481;178580480;178580479 | chr2:179445208;179445207;179445206 |
| Novex-2 | 13427 | 40504;40505;40506 | chr2:178580481;178580480;178580479 | chr2:179445208;179445207;179445206 |
| 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 | rs200343420  |
-0.093 | 0.002 | N | 0.226 | 0.059 | None | gnomAD-2.1.1 | 3.75668E-04 | None | None | None | None | I | None | 3.68164E-03 | 3.96646E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 7.83E-06 | 0 |
| V/I | rs200343420 |
-0.093 | 0.002 | N | 0.226 | 0.059 | None | gnomAD-3.1.2 | 1.00638E-03 | None | None | None | None | I | None | 3.40432E-03 | 6.55222E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 9.57854E-04 |
| V/I | rs200343420 |
-0.093 | 0.002 | N | 0.226 | 0.059 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/I | rs200343420 |
-0.093 | 0.002 | N | 0.226 | 0.059 | None | gnomAD-4.0.0 | 1.81648E-04 | None | None | None | None | I | None | 3.40127E-03 | 4.16931E-04 | None | 0 | 0 | None | 0 | 0 | 8.47897E-07 | 3.29475E-05 | 1.44185E-04 |
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 | 0.1441 | likely_benign | 0.1433 | benign | -0.765 | Destabilizing | None | N | 0.143 | neutral | N | 0.464562251 | None | None | I |
| V/C | 0.6053 | likely_pathogenic | 0.5997 | pathogenic | -0.618 | Destabilizing | 0.836 | D | 0.342 | neutral | None | None | None | None | I |
| V/D | 0.3169 | likely_benign | 0.3244 | benign | -0.713 | Destabilizing | 0.351 | N | 0.425 | neutral | N | 0.492634287 | None | None | I |
| V/E | 0.2849 | likely_benign | 0.2925 | benign | -0.809 | Destabilizing | 0.418 | N | 0.354 | neutral | None | None | None | None | I |
| V/F | 0.2223 | likely_benign | 0.2353 | benign | -0.884 | Destabilizing | 0.213 | N | 0.381 | neutral | N | 0.519898246 | None | None | I |
| V/G | 0.1521 | likely_benign | 0.1538 | benign | -0.941 | Destabilizing | 0.101 | N | 0.344 | neutral | N | 0.448440792 | None | None | I |
| V/H | 0.5672 | likely_pathogenic | 0.5621 | ambiguous | -0.522 | Destabilizing | 0.836 | D | 0.383 | neutral | None | None | None | None | I |
| V/I | 0.0843 | likely_benign | 0.0863 | benign | -0.432 | Destabilizing | 0.002 | N | 0.226 | neutral | N | 0.471162936 | None | None | I |
| V/K | 0.4014 | ambiguous | 0.3935 | ambiguous | -0.749 | Destabilizing | 0.418 | N | 0.354 | neutral | None | None | None | None | I |
| V/L | 0.2171 | likely_benign | 0.2173 | benign | -0.432 | Destabilizing | 0.017 | N | 0.213 | neutral | N | 0.492981003 | None | None | I |
| V/M | 0.1637 | likely_benign | 0.163 | benign | -0.391 | Destabilizing | 0.716 | D | 0.281 | neutral | None | None | None | None | I |
| V/N | 0.2237 | likely_benign | 0.2312 | benign | -0.428 | Destabilizing | 0.418 | N | 0.452 | neutral | None | None | None | None | I |
| V/P | 0.8197 | likely_pathogenic | 0.8191 | pathogenic | -0.508 | Destabilizing | 0.593 | D | 0.431 | neutral | None | None | None | None | I |
| V/Q | 0.309 | likely_benign | 0.3047 | benign | -0.68 | Destabilizing | 0.836 | D | 0.463 | neutral | None | None | None | None | I |
| V/R | 0.3725 | ambiguous | 0.3681 | ambiguous | -0.174 | Destabilizing | 0.418 | N | 0.479 | neutral | None | None | None | None | I |
| V/S | 0.1604 | likely_benign | 0.1612 | benign | -0.773 | Destabilizing | 0.012 | N | 0.196 | neutral | None | None | None | None | I |
| V/T | 0.129 | likely_benign | 0.1321 | benign | -0.77 | Destabilizing | 0.129 | N | 0.227 | neutral | None | None | None | None | I |
| V/W | 0.8329 | likely_pathogenic | 0.8392 | pathogenic | -0.988 | Destabilizing | 0.983 | D | 0.371 | neutral | None | None | None | None | I |
| V/Y | 0.5206 | ambiguous | 0.5375 | ambiguous | -0.704 | Destabilizing | 0.01 | N | 0.258 | 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.