Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15565 | 46918;46919;46920 | chr2:178619624;178619623;178619622 | chr2:179484351;179484350;179484349 |
| N2AB | 13924 | 41995;41996;41997 | chr2:178619624;178619623;178619622 | chr2:179484351;179484350;179484349 |
| N2A | 12997 | 39214;39215;39216 | chr2:178619624;178619623;178619622 | chr2:179484351;179484350;179484349 |
| N2B | 6500 | 19723;19724;19725 | chr2:178619624;178619623;178619622 | chr2:179484351;179484350;179484349 |
| Novex-1 | 6625 | 20098;20099;20100 | chr2:178619624;178619623;178619622 | chr2:179484351;179484350;179484349 |
| Novex-2 | 6692 | 20299;20300;20301 | chr2:178619624;178619623;178619622 | chr2:179484351;179484350;179484349 |
| 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/S | rs145520397  |
-0.243 | 1.0 | N | 0.503 | 0.219 | None | gnomAD-2.1.1 | 6.06953E-04 | None | None | None | None | I | None | 6.09453E-03 | 3.71089E-04 | None | 0 | 0 | None | 0 | None | 0 | 5.5E-05 | 2.83126E-04 |
| A/S | rs145520397 |
-0.243 | 1.0 | N | 0.503 | 0.219 | None | gnomAD-3.1.2 | 1.81698E-03 | None | None | None | None | I | None | 6.03748E-03 | 1.44585E-03 | 0 | 0 | 0 | None | 0 | 0 | 2.95E-05 | 0 | 9.57854E-04 |
| A/S | rs145520397 |
-0.243 | 1.0 | N | 0.503 | 0.219 | None | 1000 genomes | 1.19808E-03 | None | None | None | None | I | None | 3E-03 | 2.9E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/S | rs145520397 |
-0.243 | 1.0 | N | 0.503 | 0.219 | None | gnomAD-4.0.0 | 3.525E-04 | None | None | None | None | I | None | 6.10457E-03 | 7.36722E-04 | None | 0 | 0 | None | 1.56402E-05 | 1.65563E-04 | 2.96968E-05 | 0 | 4.81186E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6214 | likely_pathogenic | 0.6207 | pathogenic | -0.721 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| A/D | 0.6432 | likely_pathogenic | 0.7385 | pathogenic | -0.617 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | I |
| A/E | 0.4942 | ambiguous | 0.5986 | pathogenic | -0.751 | Destabilizing | 1.0 | D | 0.623 | neutral | N | 0.494863637 | None | None | I |
| A/F | 0.5003 | ambiguous | 0.5589 | ambiguous | -0.835 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| A/G | 0.2225 | likely_benign | 0.2244 | benign | -0.407 | Destabilizing | 1.0 | D | 0.478 | neutral | N | 0.500301598 | None | None | I |
| A/H | 0.7275 | likely_pathogenic | 0.7715 | pathogenic | -0.394 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| A/I | 0.386 | ambiguous | 0.4967 | ambiguous | -0.301 | Destabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | I |
| A/K | 0.688 | likely_pathogenic | 0.7487 | pathogenic | -0.774 | Destabilizing | 1.0 | D | 0.622 | neutral | None | None | None | None | I |
| A/L | 0.3097 | likely_benign | 0.3643 | ambiguous | -0.301 | Destabilizing | 1.0 | D | 0.555 | neutral | None | None | None | None | I |
| A/M | 0.3731 | ambiguous | 0.4912 | ambiguous | -0.425 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| A/N | 0.5469 | ambiguous | 0.6241 | pathogenic | -0.422 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| A/P | 0.8471 | likely_pathogenic | 0.8574 | pathogenic | -0.275 | Destabilizing | 1.0 | D | 0.635 | neutral | N | 0.500992555 | None | None | I |
| A/Q | 0.517 | ambiguous | 0.5789 | pathogenic | -0.687 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | I |
| A/R | 0.6326 | likely_pathogenic | 0.6741 | pathogenic | -0.281 | Destabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | I |
| A/S | 0.1404 | likely_benign | 0.1705 | benign | -0.616 | Destabilizing | 1.0 | D | 0.503 | neutral | N | 0.497373388 | None | None | I |
| A/T | 0.1731 | likely_benign | 0.2216 | benign | -0.672 | Destabilizing | 1.0 | D | 0.607 | neutral | N | 0.498253831 | None | None | I |
| A/V | 0.1867 | likely_benign | 0.2499 | benign | -0.275 | Destabilizing | 1.0 | D | 0.528 | neutral | N | 0.500137535 | None | None | I |
| A/W | 0.8951 | likely_pathogenic | 0.9142 | pathogenic | -1.008 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| A/Y | 0.6857 | likely_pathogenic | 0.7364 | pathogenic | -0.657 | Destabilizing | 1.0 | D | 0.672 | 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.