Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18 | 277;278;279 | chr2:178804591;178804590;178804589 | chr2:179669318;179669317;179669316 |
| N2AB | 18 | 277;278;279 | chr2:178804591;178804590;178804589 | chr2:179669318;179669317;179669316 |
| N2A | 18 | 277;278;279 | chr2:178804591;178804590;178804589 | chr2:179669318;179669317;179669316 |
| N2B | 18 | 277;278;279 | chr2:178804591;178804590;178804589 | chr2:179669318;179669317;179669316 |
| Novex-1 | 18 | 277;278;279 | chr2:178804591;178804590;178804589 | chr2:179669318;179669317;179669316 |
| Novex-2 | 18 | 277;278;279 | chr2:178804591;178804590;178804589 | chr2:179669318;179669317;179669316 |
| Novex-3 | 18 | 277;278;279 | chr2:178804591;178804590;178804589 | chr2:179669318;179669317;179669316 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/R | rs748322000  |
-0.002 | 1.0 | N | 0.719 | 0.593 | None | gnomAD-2.1.1 | 7.08E-06 | None | None | None | -1.227(TCAP) | N | None | 8.01E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/R | rs748322000 |
-0.002 | 1.0 | N | 0.719 | 0.593 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | -1.227(TCAP) | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/R | rs748322000 |
-0.002 | 1.0 | N | 0.719 | 0.593 | None | gnomAD-4.0.0 | 7.68421E-06 | None | None | None | -1.227(TCAP) | N | None | 1.01461E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3422 | ambiguous | 0.3166 | benign | -0.722 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | -0.623(TCAP) | N |
| L/C | 0.925 | likely_pathogenic | 0.9144 | pathogenic | -0.754 | Destabilizing | 1.0 | D | 0.61 | neutral | None | None | None | -0.444(TCAP) | N |
| L/D | 0.821 | likely_pathogenic | 0.8085 | pathogenic | 0.001 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | -0.382(TCAP) | N |
| L/E | 0.4637 | ambiguous | 0.427 | ambiguous | -0.063 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | -0.472(TCAP) | N |
| L/F | 0.2905 | likely_benign | 0.2813 | benign | -0.538 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | -0.042(TCAP) | N |
| L/G | 0.6883 | likely_pathogenic | 0.6702 | pathogenic | -0.918 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | -0.602(TCAP) | N |
| L/H | 0.5332 | ambiguous | 0.4991 | ambiguous | -0.102 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | -0.115(TCAP) | N |
| L/I | 0.1821 | likely_benign | 0.183 | benign | -0.315 | Destabilizing | 0.996 | D | 0.531 | neutral | None | None | None | -0.723(TCAP) | N |
| L/K | 0.4105 | ambiguous | 0.3792 | ambiguous | -0.424 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | -0.972(TCAP) | N |
| L/M | 0.189 | likely_benign | 0.1786 | benign | -0.444 | Destabilizing | 1.0 | D | 0.585 | neutral | N | 0.443862085 | None | -0.688(TCAP) | N |
| L/N | 0.5882 | likely_pathogenic | 0.5781 | pathogenic | -0.296 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | -0.464(TCAP) | N |
| L/P | 0.3455 | ambiguous | 0.3032 | benign | -0.417 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | N | 0.403262326 | None | -0.684(TCAP) | N |
| L/Q | 0.241 | likely_benign | 0.2133 | benign | -0.471 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.464796463 | None | -0.45(TCAP) | N |
| L/R | 0.3069 | likely_benign | 0.2825 | benign | 0.104 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.463061097 | None | -1.227(TCAP) | N |
| L/S | 0.4275 | ambiguous | 0.3925 | ambiguous | -0.822 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | -0.275(TCAP) | N |
| L/T | 0.2982 | likely_benign | 0.2764 | benign | -0.771 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | -0.367(TCAP) | N |
| L/V | 0.1791 | likely_benign | 0.1671 | benign | -0.417 | Destabilizing | 0.996 | D | 0.59 | neutral | N | 0.377703648 | None | -0.684(TCAP) | N |
| L/W | 0.4895 | ambiguous | 0.486 | ambiguous | -0.55 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | -0.187(TCAP) | N |
| L/Y | 0.681 | likely_pathogenic | 0.6784 | pathogenic | -0.315 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | -0.168(TCAP) | 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.