Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15174 | 45745;45746;45747 | chr2:178621198;178621197;178621196 | chr2:179485925;179485924;179485923 |
| N2AB | 13533 | 40822;40823;40824 | chr2:178621198;178621197;178621196 | chr2:179485925;179485924;179485923 |
| N2A | 12606 | 38041;38042;38043 | chr2:178621198;178621197;178621196 | chr2:179485925;179485924;179485923 |
| N2B | 6109 | 18550;18551;18552 | chr2:178621198;178621197;178621196 | chr2:179485925;179485924;179485923 |
| Novex-1 | 6234 | 18925;18926;18927 | chr2:178621198;178621197;178621196 | chr2:179485925;179485924;179485923 |
| Novex-2 | 6301 | 19126;19127;19128 | chr2:178621198;178621197;178621196 | chr2:179485925;179485924;179485923 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs1237099029  |
-3.075 | 0.994 | N | 0.684 | 0.332 | 0.252681307341 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/G | rs1237099029 |
-3.075 | 0.994 | N | 0.684 | 0.332 | 0.252681307341 | gnomAD-4.0.0 | 5.47749E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73792E-04 | 5.39885E-06 | 0 | 1.65865E-05 |
| R/K | rs763294408 |
-1.438 | 0.987 | N | 0.609 | 0.27 | 0.251116650651 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 5.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.57E-05 | 0 |
| R/K | rs763294408 |
-1.438 | 0.987 | N | 0.609 | 0.27 | 0.251116650651 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/K | rs763294408 |
-1.438 | 0.987 | N | 0.609 | 0.27 | 0.251116650651 | gnomAD-4.0.0 | 4.96163E-06 | None | None | None | None | N | None | 0 | 3.34403E-05 | None | 0 | 0 | None | 0 | 0 | 5.08805E-06 | 0 | 0 |
| R/M | None | None | 1.0 | D | 0.73 | 0.36 | 0.307016933798 | gnomAD-4.0.0 | 6.8469E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53306E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8314 | likely_pathogenic | 0.7255 | pathogenic | -1.631 | Destabilizing | 0.996 | D | 0.653 | neutral | None | None | None | None | N |
| R/C | 0.4357 | ambiguous | 0.267 | benign | -1.826 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| R/D | 0.9817 | likely_pathogenic | 0.9649 | pathogenic | -0.954 | Destabilizing | 0.999 | D | 0.732 | prob.delet. | None | None | None | None | N |
| R/E | 0.8467 | likely_pathogenic | 0.7635 | pathogenic | -0.767 | Destabilizing | 0.992 | D | 0.61 | neutral | None | None | None | None | N |
| R/F | 0.9244 | likely_pathogenic | 0.8291 | pathogenic | -1.151 | Destabilizing | 0.999 | D | 0.82 | deleterious | None | None | None | None | N |
| R/G | 0.8159 | likely_pathogenic | 0.6952 | pathogenic | -1.974 | Destabilizing | 0.994 | D | 0.684 | prob.neutral | N | 0.441787814 | None | None | N |
| R/H | 0.2939 | likely_benign | 0.1942 | benign | -1.882 | Destabilizing | 0.46 | N | 0.43 | neutral | None | None | None | None | N |
| R/I | 0.668 | likely_pathogenic | 0.5016 | ambiguous | -0.662 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| R/K | 0.2977 | likely_benign | 0.2334 | benign | -1.46 | Destabilizing | 0.987 | D | 0.609 | neutral | N | 0.472267162 | None | None | N |
| R/L | 0.6769 | likely_pathogenic | 0.5127 | ambiguous | -0.662 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/M | 0.6671 | likely_pathogenic | 0.4944 | ambiguous | -1.08 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | D | 0.559662569 | None | None | N |
| R/N | 0.9263 | likely_pathogenic | 0.8695 | pathogenic | -1.322 | Destabilizing | 0.992 | D | 0.632 | neutral | None | None | None | None | N |
| R/P | 0.9914 | likely_pathogenic | 0.9855 | pathogenic | -0.97 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| R/Q | 0.2439 | likely_benign | 0.1756 | benign | -1.278 | Destabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| R/S | 0.9021 | likely_pathogenic | 0.8221 | pathogenic | -2.16 | Highly Destabilizing | 0.994 | D | 0.661 | neutral | N | 0.439811574 | None | None | N |
| R/T | 0.7064 | likely_pathogenic | 0.5417 | ambiguous | -1.764 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | N | 0.46132892 | None | None | N |
| R/V | 0.7204 | likely_pathogenic | 0.5819 | pathogenic | -0.97 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| R/W | 0.5631 | ambiguous | 0.3572 | ambiguous | -0.729 | Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.506794286 | None | None | N |
| R/Y | 0.7612 | likely_pathogenic | 0.5572 | ambiguous | -0.477 | Destabilizing | 0.998 | D | 0.761 | deleterious | 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.