Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14129 | 42610;42611;42612 | chr2:178634396;178634395;178634394 | chr2:179499123;179499122;179499121 |
| N2AB | 12488 | 37687;37688;37689 | chr2:178634396;178634395;178634394 | chr2:179499123;179499122;179499121 |
| N2A | 11561 | 34906;34907;34908 | chr2:178634396;178634395;178634394 | chr2:179499123;179499122;179499121 |
| N2B | 5064 | 15415;15416;15417 | chr2:178634396;178634395;178634394 | chr2:179499123;179499122;179499121 |
| Novex-1 | 5189 | 15790;15791;15792 | chr2:178634396;178634395;178634394 | chr2:179499123;179499122;179499121 |
| Novex-2 | 5256 | 15991;15992;15993 | chr2:178634396;178634395;178634394 | chr2:179499123;179499122;179499121 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | None | None | 0.996 | N | 0.501 | 0.286 | 0.388334884743 | gnomAD-4.0.0 | 1.60068E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86582E-06 | 0 | 0 |
| K/R | None | None | 0.64 | N | 0.269 | 0.182 | 0.263140351381 | gnomAD-4.0.0 | 6.85945E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53062E-05 | None | 0 | 0 | 0 | 0 | 0 |
| K/T | rs1050750556  |
None | 0.999 | N | 0.615 | 0.423 | 0.527709697666 | gnomAD-4.0.0 | 5.48756E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.20172E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.7082 | likely_pathogenic | 0.7444 | pathogenic | -0.594 | Destabilizing | 0.998 | D | 0.553 | neutral | None | None | None | None | N |
| K/C | 0.8517 | likely_pathogenic | 0.8668 | pathogenic | -0.664 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| K/D | 0.8711 | likely_pathogenic | 0.9042 | pathogenic | -0.166 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| K/E | 0.3725 | ambiguous | 0.4192 | ambiguous | -0.019 | Destabilizing | 0.996 | D | 0.501 | neutral | N | 0.503988073 | None | None | N |
| K/F | 0.9033 | likely_pathogenic | 0.9046 | pathogenic | -0.226 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| K/G | 0.7583 | likely_pathogenic | 0.8215 | pathogenic | -0.958 | Destabilizing | 1.0 | D | 0.569 | neutral | None | None | None | None | N |
| K/H | 0.5089 | ambiguous | 0.524 | ambiguous | -1.035 | Destabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | N |
| K/I | 0.5575 | ambiguous | 0.5774 | pathogenic | 0.357 | Stabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| K/L | 0.5907 | likely_pathogenic | 0.6051 | pathogenic | 0.357 | Stabilizing | 1.0 | D | 0.569 | neutral | None | None | None | None | N |
| K/M | 0.4228 | ambiguous | 0.4203 | ambiguous | -0.044 | Destabilizing | 1.0 | D | 0.643 | neutral | D | 0.571788144 | None | None | N |
| K/N | 0.6714 | likely_pathogenic | 0.7096 | pathogenic | -0.588 | Destabilizing | 0.999 | D | 0.609 | neutral | N | 0.510458866 | None | None | N |
| K/P | 0.9797 | likely_pathogenic | 0.9883 | pathogenic | 0.068 | Stabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | N |
| K/Q | 0.1965 | likely_benign | 0.2068 | benign | -0.513 | Destabilizing | 0.999 | D | 0.598 | neutral | N | 0.486373944 | None | None | N |
| K/R | 0.1036 | likely_benign | 0.1121 | benign | -0.461 | Destabilizing | 0.64 | D | 0.269 | neutral | N | 0.490476701 | None | None | N |
| K/S | 0.7411 | likely_pathogenic | 0.7812 | pathogenic | -1.172 | Destabilizing | 0.998 | D | 0.566 | neutral | None | None | None | None | N |
| K/T | 0.4682 | ambiguous | 0.5077 | ambiguous | -0.809 | Destabilizing | 0.999 | D | 0.615 | neutral | N | 0.513504287 | None | None | N |
| K/V | 0.5505 | ambiguous | 0.5805 | pathogenic | 0.068 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| K/W | 0.9088 | likely_pathogenic | 0.9175 | pathogenic | -0.18 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| K/Y | 0.8065 | likely_pathogenic | 0.8143 | pathogenic | 0.108 | Stabilizing | 1.0 | D | 0.683 | prob.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.