Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35635 | 107128;107129;107130 | chr2:178528848;178528847;178528846 | chr2:179393575;179393574;179393573 |
| N2AB | 33994 | 102205;102206;102207 | chr2:178528848;178528847;178528846 | chr2:179393575;179393574;179393573 |
| N2A | 33067 | 99424;99425;99426 | chr2:178528848;178528847;178528846 | chr2:179393575;179393574;179393573 |
| N2B | 26570 | 79933;79934;79935 | chr2:178528848;178528847;178528846 | chr2:179393575;179393574;179393573 |
| Novex-1 | 26695 | 80308;80309;80310 | chr2:178528848;178528847;178528846 | chr2:179393575;179393574;179393573 |
| Novex-2 | 26762 | 80509;80510;80511 | chr2:178528848;178528847;178528846 | chr2:179393575;179393574;179393573 |
| 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 | rs1255745337  |
0.12 | 0.001 | N | 0.128 | 0.061 | 0.110078149338 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs1255745337 |
0.12 | 0.001 | N | 0.128 | 0.061 | 0.110078149338 | gnomAD-4.0.0 | 1.3683E-06 | None | None | None | None | N | None | 0 | 2.23624E-05 | None | 0 | 0 | None | 0 | 0 | 8.99399E-07 | 0 | 0 |
| D/H | None | None | 0.773 | N | 0.441 | 0.32 | 0.254244900254 | gnomAD-4.0.0 | 6.8415E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99399E-07 | 0 | 0 |
| D/N | None | None | 0.324 | N | 0.348 | 0.213 | 0.192905019026 | gnomAD-4.0.0 | 1.3683E-06 | None | None | None | None | N | None | 2.98686E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99399E-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 | 0.2536 | likely_benign | 0.2365 | benign | -0.248 | Destabilizing | 0.09 | N | 0.418 | neutral | N | 0.468450705 | None | None | N |
| D/C | 0.8337 | likely_pathogenic | 0.8436 | pathogenic | 0.042 | Stabilizing | 0.981 | D | 0.549 | neutral | None | None | None | None | N |
| D/E | 0.2582 | likely_benign | 0.2355 | benign | -0.275 | Destabilizing | 0.001 | N | 0.128 | neutral | N | 0.436740932 | None | None | N |
| D/F | 0.803 | likely_pathogenic | 0.7913 | pathogenic | -0.281 | Destabilizing | 0.932 | D | 0.535 | neutral | None | None | None | None | N |
| D/G | 0.2395 | likely_benign | 0.2203 | benign | -0.411 | Destabilizing | 0.324 | N | 0.353 | neutral | N | 0.469144139 | None | None | N |
| D/H | 0.4659 | ambiguous | 0.4685 | ambiguous | -0.028 | Destabilizing | 0.773 | D | 0.441 | neutral | N | 0.469144139 | None | None | N |
| D/I | 0.6493 | likely_pathogenic | 0.6505 | pathogenic | 0.125 | Stabilizing | 0.818 | D | 0.539 | neutral | None | None | None | None | N |
| D/K | 0.5833 | likely_pathogenic | 0.6086 | pathogenic | 0.349 | Stabilizing | 0.241 | N | 0.35 | neutral | None | None | None | None | N |
| D/L | 0.6487 | likely_pathogenic | 0.6315 | pathogenic | 0.125 | Stabilizing | 0.69 | D | 0.489 | neutral | None | None | None | None | N |
| D/M | 0.8197 | likely_pathogenic | 0.802 | pathogenic | 0.214 | Stabilizing | 0.981 | D | 0.518 | neutral | None | None | None | None | N |
| D/N | 0.1253 | likely_benign | 0.1104 | benign | 0.124 | Stabilizing | 0.324 | N | 0.348 | neutral | N | 0.468624064 | None | None | N |
| D/P | 0.903 | likely_pathogenic | 0.9098 | pathogenic | 0.021 | Stabilizing | 0.818 | D | 0.436 | neutral | None | None | None | None | N |
| D/Q | 0.5528 | ambiguous | 0.5501 | ambiguous | 0.132 | Stabilizing | 0.019 | N | 0.242 | neutral | None | None | None | None | N |
| D/R | 0.6123 | likely_pathogenic | 0.636 | pathogenic | 0.502 | Stabilizing | 0.527 | D | 0.485 | neutral | None | None | None | None | N |
| D/S | 0.1854 | likely_benign | 0.1689 | benign | 0.016 | Stabilizing | 0.024 | N | 0.233 | neutral | None | None | None | None | N |
| D/T | 0.4165 | ambiguous | 0.4057 | ambiguous | 0.14 | Stabilizing | 0.241 | N | 0.366 | neutral | None | None | None | None | N |
| D/V | 0.4231 | ambiguous | 0.4171 | ambiguous | 0.021 | Stabilizing | 0.627 | D | 0.491 | neutral | N | 0.468624064 | None | None | N |
| D/W | 0.9559 | likely_pathogenic | 0.9591 | pathogenic | -0.181 | Destabilizing | 0.981 | D | 0.627 | neutral | None | None | None | None | N |
| D/Y | 0.399 | ambiguous | 0.4033 | ambiguous | -0.052 | Destabilizing | 0.912 | D | 0.537 | neutral | N | 0.469490855 | 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.