Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20771 | 62536;62537;62538 | chr2:178589414;178589413;178589412 | chr2:179454141;179454140;179454139 |
| N2AB | 19130 | 57613;57614;57615 | chr2:178589414;178589413;178589412 | chr2:179454141;179454140;179454139 |
| N2A | 18203 | 54832;54833;54834 | chr2:178589414;178589413;178589412 | chr2:179454141;179454140;179454139 |
| N2B | 11706 | 35341;35342;35343 | chr2:178589414;178589413;178589412 | chr2:179454141;179454140;179454139 |
| Novex-1 | 11831 | 35716;35717;35718 | chr2:178589414;178589413;178589412 | chr2:179454141;179454140;179454139 |
| Novex-2 | 11898 | 35917;35918;35919 | chr2:178589414;178589413;178589412 | chr2:179454141;179454140;179454139 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs1384039456  |
-1.134 | 0.998 | N | 0.624 | 0.286 | 0.547168864562 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| L/F | rs1384039456 |
-1.134 | 0.998 | N | 0.624 | 0.286 | 0.547168864562 | gnomAD-4.0.0 | 6.84345E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99556E-07 | 0 | 0 |
| L/R | rs2049747701 |
None | 0.999 | N | 0.71 | 0.591 | 0.850017294419 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/R | rs2049747701 |
None | 0.999 | N | 0.71 | 0.591 | 0.850017294419 | gnomAD-4.0.0 | 6.57765E-06 | None | None | None | None | N | None | 2.41441E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | None | None | 0.543 | N | 0.377 | 0.187 | 0.326074293725 | gnomAD-4.0.0 | 2.73738E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59822E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9013 | likely_pathogenic | 0.9098 | pathogenic | -2.104 | Highly Destabilizing | 0.992 | D | 0.488 | neutral | None | None | None | None | N |
| L/C | 0.9039 | likely_pathogenic | 0.9281 | pathogenic | -1.357 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| L/D | 0.9992 | likely_pathogenic | 0.9994 | pathogenic | -1.769 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| L/E | 0.9947 | likely_pathogenic | 0.9958 | pathogenic | -1.623 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| L/F | 0.7821 | likely_pathogenic | 0.7863 | pathogenic | -1.181 | Destabilizing | 0.998 | D | 0.624 | neutral | N | 0.512742987 | None | None | N |
| L/G | 0.9897 | likely_pathogenic | 0.9914 | pathogenic | -2.58 | Highly Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| L/H | 0.9939 | likely_pathogenic | 0.9947 | pathogenic | -1.875 | Destabilizing | 1.0 | D | 0.744 | deleterious | D | 0.525147431 | None | None | N |
| L/I | 0.1353 | likely_benign | 0.1327 | benign | -0.782 | Destabilizing | 0.543 | D | 0.285 | neutral | N | 0.469698712 | None | None | N |
| L/K | 0.9922 | likely_pathogenic | 0.9934 | pathogenic | -1.499 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| L/M | 0.3283 | likely_benign | 0.3679 | ambiguous | -0.718 | Destabilizing | 0.999 | D | 0.634 | neutral | None | None | None | None | N |
| L/N | 0.996 | likely_pathogenic | 0.9967 | pathogenic | -1.577 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| L/P | 0.9883 | likely_pathogenic | 0.9894 | pathogenic | -1.197 | Destabilizing | 0.999 | D | 0.742 | deleterious | D | 0.525147431 | None | None | N |
| L/Q | 0.9868 | likely_pathogenic | 0.9894 | pathogenic | -1.552 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| L/R | 0.9866 | likely_pathogenic | 0.9874 | pathogenic | -1.134 | Destabilizing | 0.999 | D | 0.71 | prob.delet. | N | 0.506789687 | None | None | N |
| L/S | 0.9917 | likely_pathogenic | 0.993 | pathogenic | -2.309 | Highly Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | N |
| L/T | 0.9299 | likely_pathogenic | 0.9385 | pathogenic | -2.027 | Highly Destabilizing | 0.998 | D | 0.613 | neutral | None | None | None | None | N |
| L/V | 0.1855 | likely_benign | 0.1909 | benign | -1.197 | Destabilizing | 0.543 | D | 0.377 | neutral | N | 0.481334236 | None | None | N |
| L/W | 0.9823 | likely_pathogenic | 0.9786 | pathogenic | -1.432 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| L/Y | 0.9874 | likely_pathogenic | 0.9866 | pathogenic | -1.151 | Destabilizing | 1.0 | D | 0.672 | 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.