Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 972 | 3139;3140;3141 | chr2:178782992;178782991;178782990 | chr2:179647719;179647718;179647717 |
| N2AB | 972 | 3139;3140;3141 | chr2:178782992;178782991;178782990 | chr2:179647719;179647718;179647717 |
| N2A | 972 | 3139;3140;3141 | chr2:178782992;178782991;178782990 | chr2:179647719;179647718;179647717 |
| N2B | 926 | 3001;3002;3003 | chr2:178782992;178782991;178782990 | chr2:179647719;179647718;179647717 |
| Novex-1 | 926 | 3001;3002;3003 | chr2:178782992;178782991;178782990 | chr2:179647719;179647718;179647717 |
| Novex-2 | 926 | 3001;3002;3003 | chr2:178782992;178782991;178782990 | chr2:179647719;179647718;179647717 |
| Novex-3 | 972 | 3139;3140;3141 | chr2:178782992;178782991;178782990 | chr2:179647719;179647718;179647717 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs540920622  |
-0.687 | 1.0 | D | 0.844 | 0.578 | 0.885469739524 | gnomAD-2.1.1 | 7.98E-06 | None | None | None | None | I | None | 6.19E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| P/L | rs540920622 |
-0.687 | 1.0 | D | 0.844 | 0.578 | 0.885469739524 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs540920622 |
-0.687 | 1.0 | D | 0.844 | 0.578 | 0.885469739524 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| P/L | rs540920622 |
-0.687 | 1.0 | D | 0.844 | 0.578 | 0.885469739524 | gnomAD-4.0.0 | 4.33687E-06 | None | None | None | None | I | None | 1.33291E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23736E-06 | 1.09796E-05 | 0 |
| P/Q | rs540920622 |
None | 1.0 | D | 0.852 | 0.569 | 0.751870096423 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/Q | rs540920622 |
None | 1.0 | D | 0.852 | 0.569 | 0.751870096423 | gnomAD-4.0.0 | 6.57307E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46998E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.8514 | likely_pathogenic | 0.8916 | pathogenic | -1.783 | Destabilizing | 1.0 | D | 0.816 | deleterious | D | 0.660086112 | None | None | I |
| P/C | 0.9933 | likely_pathogenic | 0.9957 | pathogenic | -1.483 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | I |
| P/D | 0.999 | likely_pathogenic | 0.9993 | pathogenic | -1.578 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | I |
| P/E | 0.9967 | likely_pathogenic | 0.9978 | pathogenic | -1.496 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | I |
| P/F | 0.9985 | likely_pathogenic | 0.9991 | pathogenic | -1.301 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| P/G | 0.9923 | likely_pathogenic | 0.9948 | pathogenic | -2.192 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | I |
| P/H | 0.9951 | likely_pathogenic | 0.9971 | pathogenic | -1.774 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| P/I | 0.9805 | likely_pathogenic | 0.9854 | pathogenic | -0.721 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | I |
| P/K | 0.9978 | likely_pathogenic | 0.9986 | pathogenic | -1.339 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | I |
| P/L | 0.9446 | likely_pathogenic | 0.9633 | pathogenic | -0.721 | Destabilizing | 1.0 | D | 0.844 | deleterious | D | 0.70959858 | None | None | I |
| P/M | 0.9912 | likely_pathogenic | 0.994 | pathogenic | -0.732 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| P/N | 0.9982 | likely_pathogenic | 0.9987 | pathogenic | -1.303 | Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | I |
| P/Q | 0.9926 | likely_pathogenic | 0.9956 | pathogenic | -1.362 | Destabilizing | 1.0 | D | 0.852 | deleterious | D | 0.796149271 | None | None | I |
| P/R | 0.9934 | likely_pathogenic | 0.9962 | pathogenic | -0.998 | Destabilizing | 1.0 | D | 0.835 | deleterious | D | 0.82946263 | None | None | I |
| P/S | 0.9775 | likely_pathogenic | 0.9867 | pathogenic | -1.966 | Destabilizing | 1.0 | D | 0.867 | deleterious | D | 0.828472894 | None | None | I |
| P/T | 0.965 | likely_pathogenic | 0.9781 | pathogenic | -1.752 | Destabilizing | 1.0 | D | 0.862 | deleterious | D | 0.747802185 | None | None | I |
| P/V | 0.9528 | likely_pathogenic | 0.9642 | pathogenic | -1.042 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | I |
| P/W | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -1.552 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| P/Y | 0.9992 | likely_pathogenic | 0.9995 | pathogenic | -1.217 | Destabilizing | 1.0 | D | 0.8 | deleterious | 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.