Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16170 | 48733;48734;48735 | chr2:178615437;178615436;178615435 | chr2:179480164;179480163;179480162 |
| N2AB | 14529 | 43810;43811;43812 | chr2:178615437;178615436;178615435 | chr2:179480164;179480163;179480162 |
| N2A | 13602 | 41029;41030;41031 | chr2:178615437;178615436;178615435 | chr2:179480164;179480163;179480162 |
| N2B | 7105 | 21538;21539;21540 | chr2:178615437;178615436;178615435 | chr2:179480164;179480163;179480162 |
| Novex-1 | 7230 | 21913;21914;21915 | chr2:178615437;178615436;178615435 | chr2:179480164;179480163;179480162 |
| Novex-2 | 7297 | 22114;22115;22116 | chr2:178615437;178615436;178615435 | chr2:179480164;179480163;179480162 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs370809363  |
-0.046 | None | N | 0.022 | 0.08 | None | gnomAD-2.1.1 | 6.44E-05 | None | None | None | None | I | None | 7.03701E-04 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/S | rs370809363 |
-0.046 | None | N | 0.022 | 0.08 | None | gnomAD-3.1.2 | 2.3033E-04 | None | None | None | None | I | None | 8.20543E-04 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs370809363 |
-0.046 | None | N | 0.022 | 0.08 | None | gnomAD-4.0.0 | 4.77502E-05 | None | None | None | None | I | None | 8.00576E-04 | 5.00434E-05 | None | 0 | 2.23394E-05 | None | 0 | 1.65453E-04 | 6.7855E-06 | 0 | 6.40902E-05 |
| N/T | rs370809363 |
0.081 | 0.003 | N | 0.161 | 0.117 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.45E-05 | 0 |
| N/T | rs370809363 |
0.081 | 0.003 | N | 0.161 | 0.117 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/T | rs370809363 |
0.081 | 0.003 | N | 0.161 | 0.117 | None | gnomAD-4.0.0 | 2.10861E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.88382E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.1919 | likely_benign | 0.1889 | benign | -0.613 | Destabilizing | 0.002 | N | 0.181 | neutral | None | None | None | None | I |
| N/C | 0.3268 | likely_benign | 0.3255 | benign | 0.258 | Stabilizing | 0.497 | N | 0.311 | neutral | None | None | None | None | I |
| N/D | 0.1531 | likely_benign | 0.1303 | benign | -0.393 | Destabilizing | 0.014 | N | 0.185 | neutral | N | 0.405390549 | None | None | I |
| N/E | 0.2688 | likely_benign | 0.2719 | benign | -0.427 | Destabilizing | 0.004 | N | 0.125 | neutral | None | None | None | None | I |
| N/F | 0.6262 | likely_pathogenic | 0.6415 | pathogenic | -1.061 | Destabilizing | 0.497 | N | 0.4 | neutral | None | None | None | None | I |
| N/G | 0.2249 | likely_benign | 0.2089 | benign | -0.77 | Destabilizing | 0.008 | N | 0.125 | neutral | None | None | None | None | I |
| N/H | 0.1046 | likely_benign | 0.0923 | benign | -0.898 | Destabilizing | 0.196 | N | 0.282 | neutral | N | 0.485845495 | None | None | I |
| N/I | 0.4105 | ambiguous | 0.4418 | ambiguous | -0.279 | Destabilizing | 0.065 | N | 0.419 | neutral | D | 0.596813545 | None | None | I |
| N/K | 0.1174 | likely_benign | 0.1195 | benign | 0.123 | Stabilizing | None | N | 0.019 | neutral | N | 0.45578346 | None | None | I |
| N/L | 0.2814 | likely_benign | 0.3112 | benign | -0.279 | Destabilizing | 0.018 | N | 0.245 | neutral | None | None | None | None | I |
| N/M | 0.331 | likely_benign | 0.3734 | ambiguous | 0.438 | Stabilizing | 0.497 | N | 0.317 | neutral | None | None | None | None | I |
| N/P | 0.8913 | likely_pathogenic | 0.899 | pathogenic | -0.367 | Destabilizing | 0.085 | N | 0.303 | neutral | None | None | None | None | I |
| N/Q | 0.1864 | likely_benign | 0.1878 | benign | -0.563 | Destabilizing | 0.009 | N | 0.171 | neutral | None | None | None | None | I |
| N/R | 0.149 | likely_benign | 0.1501 | benign | 0.284 | Stabilizing | None | N | 0.05 | neutral | None | None | None | None | I |
| N/S | 0.0793 | likely_benign | 0.0726 | benign | -0.208 | Destabilizing | None | N | 0.022 | neutral | N | 0.406965338 | None | None | I |
| N/T | 0.0949 | likely_benign | 0.0993 | benign | -0.107 | Destabilizing | 0.003 | N | 0.161 | neutral | N | 0.413440491 | None | None | I |
| N/V | 0.3182 | likely_benign | 0.3467 | ambiguous | -0.367 | Destabilizing | 0.018 | N | 0.257 | neutral | None | None | None | None | I |
| N/W | 0.8295 | likely_pathogenic | 0.8316 | pathogenic | -0.954 | Destabilizing | 0.788 | D | 0.302 | neutral | None | None | None | None | I |
| N/Y | 0.2608 | likely_benign | 0.236 | benign | -0.69 | Destabilizing | 0.196 | N | 0.384 | neutral | D | 0.531304127 | 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.