Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28891 | 86896;86897;86898 | chr2:178559461;178559460;178559459 | chr2:179424188;179424187;179424186 |
| N2AB | 27250 | 81973;81974;81975 | chr2:178559461;178559460;178559459 | chr2:179424188;179424187;179424186 |
| N2A | 26323 | 79192;79193;79194 | chr2:178559461;178559460;178559459 | chr2:179424188;179424187;179424186 |
| N2B | 19826 | 59701;59702;59703 | chr2:178559461;178559460;178559459 | chr2:179424188;179424187;179424186 |
| Novex-1 | 19951 | 60076;60077;60078 | chr2:178559461;178559460;178559459 | chr2:179424188;179424187;179424186 |
| Novex-2 | 20018 | 60277;60278;60279 | chr2:178559461;178559460;178559459 | chr2:179424188;179424187;179424186 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs535801518  |
-0.281 | 0.314 | N | 0.318 | 0.157 | 0.200317383148 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| A/P | rs535801518 |
-0.281 | 0.314 | N | 0.318 | 0.157 | 0.200317383148 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| A/P | rs535801518 |
-0.281 | 0.314 | N | 0.318 | 0.157 | 0.200317383148 | gnomAD-4.0.0 | 1.31349E-05 | None | None | None | None | N | None | 2.40535E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07555E-04 | 0 |
| A/S | rs535801518 |
None | None | N | 0.269 | 0.093 | 0.124217242631 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/S | rs535801518 |
None | None | N | 0.269 | 0.093 | 0.124217242631 | gnomAD-4.0.0 | 2.54087E-05 | None | None | None | None | N | None | 1.3349E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39058E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.814 | likely_pathogenic | 0.7733 | pathogenic | -0.643 | Destabilizing | 0.823 | D | 0.376 | neutral | None | None | None | None | N |
| A/D | 0.945 | likely_pathogenic | 0.8995 | pathogenic | -0.661 | Destabilizing | 0.08 | N | 0.363 | neutral | None | None | None | None | N |
| A/E | 0.9249 | likely_pathogenic | 0.8698 | pathogenic | -0.751 | Destabilizing | 0.084 | N | 0.27 | neutral | N | 0.428376872 | None | None | N |
| A/F | 0.791 | likely_pathogenic | 0.7419 | pathogenic | -0.807 | Destabilizing | 0.821 | D | 0.424 | neutral | None | None | None | None | N |
| A/G | 0.2282 | likely_benign | 0.2159 | benign | -0.615 | Destabilizing | None | N | 0.163 | neutral | N | 0.397267319 | None | None | N |
| A/H | 0.919 | likely_pathogenic | 0.8851 | pathogenic | -0.589 | Destabilizing | 0.945 | D | 0.433 | neutral | None | None | None | None | N |
| A/I | 0.7078 | likely_pathogenic | 0.6263 | pathogenic | -0.281 | Destabilizing | 0.694 | D | 0.325 | neutral | None | None | None | None | N |
| A/K | 0.9707 | likely_pathogenic | 0.9528 | pathogenic | -0.843 | Destabilizing | 0.244 | N | 0.267 | neutral | None | None | None | None | N |
| A/L | 0.5426 | ambiguous | 0.484 | ambiguous | -0.281 | Destabilizing | 0.244 | N | 0.268 | neutral | None | None | None | None | N |
| A/M | 0.575 | likely_pathogenic | 0.5165 | ambiguous | -0.431 | Destabilizing | 0.981 | D | 0.337 | neutral | None | None | None | None | N |
| A/N | 0.6921 | likely_pathogenic | 0.6278 | pathogenic | -0.514 | Destabilizing | 0.034 | N | 0.366 | neutral | None | None | None | None | N |
| A/P | 0.8609 | likely_pathogenic | 0.8185 | pathogenic | -0.31 | Destabilizing | 0.314 | N | 0.318 | neutral | N | 0.496066089 | None | None | N |
| A/Q | 0.8154 | likely_pathogenic | 0.7713 | pathogenic | -0.724 | Destabilizing | 0.694 | D | 0.328 | neutral | None | None | None | None | N |
| A/R | 0.9417 | likely_pathogenic | 0.917 | pathogenic | -0.404 | Destabilizing | 0.694 | D | 0.325 | neutral | None | None | None | None | N |
| A/S | 0.13 | likely_benign | 0.1172 | benign | -0.743 | Destabilizing | None | N | 0.269 | neutral | N | 0.441383455 | None | None | N |
| A/T | 0.2451 | likely_benign | 0.1965 | benign | -0.748 | Destabilizing | None | N | 0.267 | neutral | N | 0.408273746 | None | None | N |
| A/V | 0.4256 | ambiguous | 0.3427 | ambiguous | -0.31 | Destabilizing | 0.084 | N | 0.329 | neutral | N | 0.45098716 | None | None | N |
| A/W | 0.9732 | likely_pathogenic | 0.9621 | pathogenic | -1.037 | Destabilizing | 0.981 | D | 0.553 | neutral | None | None | None | None | N |
| A/Y | 0.8906 | likely_pathogenic | 0.8519 | pathogenic | -0.664 | Destabilizing | 0.821 | D | 0.431 | 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.