Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23020 | 69283;69284;69285 | chr2:178577277;178577276;178577275 | chr2:179442004;179442003;179442002 |
| N2AB | 21379 | 64360;64361;64362 | chr2:178577277;178577276;178577275 | chr2:179442004;179442003;179442002 |
| N2A | 20452 | 61579;61580;61581 | chr2:178577277;178577276;178577275 | chr2:179442004;179442003;179442002 |
| N2B | 13955 | 42088;42089;42090 | chr2:178577277;178577276;178577275 | chr2:179442004;179442003;179442002 |
| Novex-1 | 14080 | 42463;42464;42465 | chr2:178577277;178577276;178577275 | chr2:179442004;179442003;179442002 |
| Novex-2 | 14147 | 42664;42665;42666 | chr2:178577277;178577276;178577275 | chr2:179442004;179442003;179442002 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | None | None | 0.011 | N | 0.353 | 0.144 | 0.357929162469 | gnomAD-4.0.0 | 1.59241E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.027E-05 |
| I/N | None | None | 0.994 | N | 0.861 | 0.573 | 0.729413103106 | gnomAD-4.0.0 | 1.36884E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79925E-06 | 0 | 0 |
| I/S | None | None | 0.983 | N | 0.811 | 0.56 | 0.74021432234 | gnomAD-4.0.0 | 6.84419E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15953E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9467 | likely_pathogenic | 0.9287 | pathogenic | -2.017 | Highly Destabilizing | 0.916 | D | 0.753 | deleterious | None | None | None | None | N |
| I/C | 0.9652 | likely_pathogenic | 0.9556 | pathogenic | -1.706 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | N |
| I/D | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -1.522 | Destabilizing | 0.996 | D | 0.86 | deleterious | None | None | None | None | N |
| I/E | 0.9977 | likely_pathogenic | 0.9977 | pathogenic | -1.413 | Destabilizing | 0.987 | D | 0.857 | deleterious | None | None | None | None | N |
| I/F | 0.7205 | likely_pathogenic | 0.6796 | pathogenic | -1.374 | Destabilizing | 0.967 | D | 0.651 | neutral | N | 0.488697847 | None | None | N |
| I/G | 0.996 | likely_pathogenic | 0.9944 | pathogenic | -2.437 | Highly Destabilizing | 0.987 | D | 0.856 | deleterious | None | None | None | None | N |
| I/H | 0.9972 | likely_pathogenic | 0.9966 | pathogenic | -1.715 | Destabilizing | 0.999 | D | 0.849 | deleterious | None | None | None | None | N |
| I/K | 0.9943 | likely_pathogenic | 0.9939 | pathogenic | -1.212 | Destabilizing | 0.987 | D | 0.856 | deleterious | None | None | None | None | N |
| I/L | 0.1952 | likely_benign | 0.187 | benign | -0.871 | Destabilizing | 0.011 | N | 0.353 | neutral | N | 0.420690391 | None | None | N |
| I/M | 0.2893 | likely_benign | 0.2773 | benign | -0.97 | Destabilizing | 0.967 | D | 0.631 | neutral | N | 0.457617898 | None | None | N |
| I/N | 0.9898 | likely_pathogenic | 0.9898 | pathogenic | -1.248 | Destabilizing | 0.994 | D | 0.861 | deleterious | N | 0.490218784 | None | None | N |
| I/P | 0.9983 | likely_pathogenic | 0.998 | pathogenic | -1.227 | Destabilizing | 0.996 | D | 0.861 | deleterious | None | None | None | None | N |
| I/Q | 0.9948 | likely_pathogenic | 0.9944 | pathogenic | -1.304 | Destabilizing | 0.996 | D | 0.867 | deleterious | None | None | None | None | N |
| I/R | 0.9914 | likely_pathogenic | 0.9904 | pathogenic | -0.855 | Destabilizing | 0.987 | D | 0.859 | deleterious | None | None | None | None | N |
| I/S | 0.9876 | likely_pathogenic | 0.9858 | pathogenic | -2.04 | Highly Destabilizing | 0.983 | D | 0.811 | deleterious | N | 0.489965294 | None | None | N |
| I/T | 0.9726 | likely_pathogenic | 0.9691 | pathogenic | -1.795 | Destabilizing | 0.967 | D | 0.752 | deleterious | N | 0.489711805 | None | None | N |
| I/V | 0.1164 | likely_benign | 0.0981 | benign | -1.227 | Destabilizing | 0.426 | N | 0.291 | neutral | N | 0.463171732 | None | None | N |
| I/W | 0.9964 | likely_pathogenic | 0.9954 | pathogenic | -1.5 | Destabilizing | 0.999 | D | 0.831 | deleterious | None | None | None | None | N |
| I/Y | 0.9799 | likely_pathogenic | 0.976 | pathogenic | -1.223 | Destabilizing | 0.987 | D | 0.735 | prob.delet. | 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.