Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28888 | 86887;86888;86889 | chr2:178559470;178559469;178559468 | chr2:179424197;179424196;179424195 |
| N2AB | 27247 | 81964;81965;81966 | chr2:178559470;178559469;178559468 | chr2:179424197;179424196;179424195 |
| N2A | 26320 | 79183;79184;79185 | chr2:178559470;178559469;178559468 | chr2:179424197;179424196;179424195 |
| N2B | 19823 | 59692;59693;59694 | chr2:178559470;178559469;178559468 | chr2:179424197;179424196;179424195 |
| Novex-1 | 19948 | 60067;60068;60069 | chr2:178559470;178559469;178559468 | chr2:179424197;179424196;179424195 |
| Novex-2 | 20015 | 60268;60269;60270 | chr2:178559470;178559469;178559468 | chr2:179424197;179424196;179424195 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs1197285138  |
-0.385 | 0.822 | N | 0.291 | 0.239 | 0.134241683229 | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11495E-04 | None | 0 | None | 0 | 0 | 0 |
| S/G | rs1197285138 |
-0.385 | 0.822 | N | 0.291 | 0.239 | 0.134241683229 | gnomAD-4.0.0 | 4.77444E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.54816E-05 | None | 0 | 0 | 2.85874E-06 | 0 | 0 |
| S/R | None | None | 0.942 | N | 0.352 | 0.356 | 0.259761712551 | gnomAD-4.0.0 | 1.59152E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02407E-05 |
| S/T | rs1470114541 |
-0.238 | 0.058 | N | 0.214 | 0.052 | 0.101711395817 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| S/T | rs1470114541 |
-0.238 | 0.058 | N | 0.214 | 0.052 | 0.101711395817 | gnomAD-4.0.0 | 1.59152E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77469E-05 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1029 | likely_benign | 0.1065 | benign | -0.135 | Destabilizing | 0.717 | D | 0.345 | neutral | None | None | None | None | N |
| S/C | 0.2509 | likely_benign | 0.2499 | benign | -0.514 | Destabilizing | 0.997 | D | 0.422 | neutral | N | 0.46869944 | None | None | N |
| S/D | 0.8041 | likely_pathogenic | 0.7871 | pathogenic | -0.127 | Destabilizing | 0.754 | D | 0.27 | neutral | None | None | None | None | N |
| S/E | 0.8545 | likely_pathogenic | 0.8421 | pathogenic | -0.234 | Destabilizing | 0.019 | N | 0.221 | neutral | None | None | None | None | N |
| S/F | 0.5324 | ambiguous | 0.5414 | ambiguous | -0.88 | Destabilizing | 0.993 | D | 0.514 | neutral | None | None | None | None | N |
| S/G | 0.1172 | likely_benign | 0.1122 | benign | -0.169 | Destabilizing | 0.822 | D | 0.291 | neutral | N | 0.434937485 | None | None | N |
| S/H | 0.7419 | likely_pathogenic | 0.7391 | pathogenic | -0.422 | Destabilizing | 0.994 | D | 0.357 | neutral | None | None | None | None | N |
| S/I | 0.4504 | ambiguous | 0.4314 | ambiguous | -0.176 | Destabilizing | 0.942 | D | 0.501 | neutral | N | 0.516769435 | None | None | N |
| S/K | 0.9459 | likely_pathogenic | 0.9388 | pathogenic | -0.473 | Destabilizing | 0.754 | D | 0.271 | neutral | None | None | None | None | N |
| S/L | 0.17 | likely_benign | 0.1696 | benign | -0.176 | Destabilizing | 0.86 | D | 0.387 | neutral | None | None | None | None | N |
| S/M | 0.3433 | ambiguous | 0.3414 | ambiguous | -0.241 | Destabilizing | 0.998 | D | 0.364 | neutral | None | None | None | None | N |
| S/N | 0.2956 | likely_benign | 0.2832 | benign | -0.275 | Destabilizing | 0.822 | D | 0.328 | neutral | N | 0.473359801 | None | None | N |
| S/P | 0.6244 | likely_pathogenic | 0.6376 | pathogenic | -0.139 | Destabilizing | 0.978 | D | 0.351 | neutral | None | None | None | None | N |
| S/Q | 0.799 | likely_pathogenic | 0.7919 | pathogenic | -0.492 | Destabilizing | 0.915 | D | 0.283 | neutral | None | None | None | None | N |
| S/R | 0.9265 | likely_pathogenic | 0.9129 | pathogenic | -0.183 | Destabilizing | 0.942 | D | 0.352 | neutral | N | 0.483059506 | None | None | N |
| S/T | 0.0959 | likely_benign | 0.1049 | benign | -0.378 | Destabilizing | 0.058 | N | 0.214 | neutral | N | 0.436364424 | None | None | N |
| S/V | 0.3634 | ambiguous | 0.3619 | ambiguous | -0.139 | Destabilizing | 0.86 | D | 0.406 | neutral | None | None | None | None | N |
| S/W | 0.6991 | likely_pathogenic | 0.6879 | pathogenic | -0.982 | Destabilizing | 0.998 | D | 0.666 | neutral | None | None | None | None | N |
| S/Y | 0.5482 | ambiguous | 0.5461 | ambiguous | -0.662 | Destabilizing | 0.993 | D | 0.505 | 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.