Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21631 | 65116;65117;65118 | chr2:178584750;178584749;178584748 | chr2:179449477;179449476;179449475 |
| N2AB | 19990 | 60193;60194;60195 | chr2:178584750;178584749;178584748 | chr2:179449477;179449476;179449475 |
| N2A | 19063 | 57412;57413;57414 | chr2:178584750;178584749;178584748 | chr2:179449477;179449476;179449475 |
| N2B | 12566 | 37921;37922;37923 | chr2:178584750;178584749;178584748 | chr2:179449477;179449476;179449475 |
| Novex-1 | 12691 | 38296;38297;38298 | chr2:178584750;178584749;178584748 | chr2:179449477;179449476;179449475 |
| Novex-2 | 12758 | 38497;38498;38499 | chr2:178584750;178584749;178584748 | chr2:179449477;179449476;179449475 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs757787828  |
-0.609 | None | N | 0.395 | 0.135 | 0.101711395817 | gnomAD-4.0.0 | 3.4216E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87259E-05 | 0 | 3.5984E-06 | 0 | 0 |
| I/M | None | None | None | N | 0.321 | 0.052 | 0.21737058555 | gnomAD-4.0.0 | 1.59187E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85956E-06 | 0 | 0 |
| I/V | None | None | None | N | 0.18 | 0.163 | 0.187945064343 | gnomAD-4.0.0 | 2.05296E-06 | None | None | None | None | N | None | 2.98972E-05 | 0 | None | 0 | 0 | None | 0 | 1.73551E-04 | 0 | 0 | 1.65717E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2032 | likely_benign | 0.1932 | benign | -2.376 | Highly Destabilizing | 0.002 | N | 0.479 | neutral | None | None | None | None | N |
| I/C | 0.4096 | ambiguous | 0.3737 | ambiguous | -1.407 | Destabilizing | None | N | 0.468 | neutral | None | None | None | None | N |
| I/D | 0.615 | likely_pathogenic | 0.6147 | pathogenic | -2.929 | Highly Destabilizing | 0.044 | N | 0.625 | neutral | None | None | None | None | N |
| I/E | 0.4149 | ambiguous | 0.4315 | ambiguous | -2.679 | Highly Destabilizing | 0.044 | N | 0.619 | neutral | None | None | None | None | N |
| I/F | 0.1411 | likely_benign | 0.1332 | benign | -1.364 | Destabilizing | 0.033 | N | 0.551 | neutral | N | 0.49383386 | None | None | N |
| I/G | 0.4405 | ambiguous | 0.4157 | ambiguous | -2.91 | Highly Destabilizing | None | N | 0.514 | neutral | None | None | None | None | N |
| I/H | 0.3183 | likely_benign | 0.313 | benign | -2.574 | Highly Destabilizing | 0.497 | N | 0.599 | neutral | None | None | None | None | N |
| I/K | 0.2666 | likely_benign | 0.2802 | benign | -1.648 | Destabilizing | 0.018 | N | 0.599 | neutral | None | None | None | None | N |
| I/L | 0.0727 | likely_benign | 0.0764 | benign | -0.808 | Destabilizing | None | N | 0.395 | neutral | N | 0.455776905 | None | None | N |
| I/M | 0.0699 | likely_benign | 0.0719 | benign | -0.782 | Destabilizing | None | N | 0.321 | neutral | N | 0.484849018 | None | None | N |
| I/N | 0.2116 | likely_benign | 0.1875 | benign | -2.082 | Highly Destabilizing | 0.033 | N | 0.624 | neutral | N | 0.491926919 | None | None | N |
| I/P | 0.9429 | likely_pathogenic | 0.942 | pathogenic | -1.316 | Destabilizing | 0.22 | N | 0.615 | neutral | None | None | None | None | N |
| I/Q | 0.2451 | likely_benign | 0.256 | benign | -1.877 | Destabilizing | 0.044 | N | 0.634 | neutral | None | None | None | None | N |
| I/R | 0.1958 | likely_benign | 0.2089 | benign | -1.523 | Destabilizing | 0.044 | N | 0.617 | neutral | None | None | None | None | N |
| I/S | 0.1607 | likely_benign | 0.1484 | benign | -2.665 | Highly Destabilizing | 0.001 | N | 0.459 | neutral | N | 0.44973358 | None | None | N |
| I/T | 0.1437 | likely_benign | 0.1257 | benign | -2.282 | Highly Destabilizing | None | N | 0.365 | neutral | N | 0.446807918 | None | None | N |
| I/V | 0.0671 | likely_benign | 0.0616 | benign | -1.316 | Destabilizing | None | N | 0.18 | neutral | N | 0.441095454 | None | None | N |
| I/W | 0.678 | likely_pathogenic | 0.6894 | pathogenic | -1.872 | Destabilizing | 0.788 | D | 0.617 | neutral | None | None | None | None | N |
| I/Y | 0.3297 | likely_benign | 0.3412 | ambiguous | -1.559 | Destabilizing | 0.085 | N | 0.634 | 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.