Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2663 | 8212;8213;8214 | chr2:178771340;178771339;178771338 | chr2:179636067;179636066;179636065 |
| N2AB | 2663 | 8212;8213;8214 | chr2:178771340;178771339;178771338 | chr2:179636067;179636066;179636065 |
| N2A | 2663 | 8212;8213;8214 | chr2:178771340;178771339;178771338 | chr2:179636067;179636066;179636065 |
| N2B | 2617 | 8074;8075;8076 | chr2:178771340;178771339;178771338 | chr2:179636067;179636066;179636065 |
| Novex-1 | 2617 | 8074;8075;8076 | chr2:178771340;178771339;178771338 | chr2:179636067;179636066;179636065 |
| Novex-2 | 2617 | 8074;8075;8076 | chr2:178771340;178771339;178771338 | chr2:179636067;179636066;179636065 |
| Novex-3 | 2663 | 8212;8213;8214 | chr2:178771340;178771339;178771338 | chr2:179636067;179636066;179636065 |
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/D | rs372885019  |
0.29 | None | N | 0.111 | 0.105 | None | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.8E-06 | 0 |
| N/D | rs372885019 |
0.29 | None | N | 0.111 | 0.105 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/D | rs372885019 |
0.29 | None | N | 0.111 | 0.105 | None | gnomAD-4.0.0 | 3.84198E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17528E-06 | 0 | 0 |
| N/S | rs1184494680 |
0.258 | 0.012 | N | 0.289 | 0.16 | 0.0611884634855 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| N/S | rs1184494680 |
0.258 | 0.012 | N | 0.289 | 0.16 | 0.0611884634855 | gnomAD-4.0.0 | 1.59057E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77454E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.128 | likely_benign | 0.131 | benign | -0.095 | Destabilizing | 0.016 | N | 0.258 | neutral | None | None | None | None | N |
| N/C | 0.2794 | likely_benign | 0.2921 | benign | 0.167 | Stabilizing | 0.864 | D | 0.319 | neutral | None | None | None | None | N |
| N/D | 0.0776 | likely_benign | 0.0818 | benign | -0.002 | Destabilizing | None | N | 0.111 | neutral | N | 0.290203347 | None | None | N |
| N/E | 0.1627 | likely_benign | 0.172 | benign | -0.073 | Destabilizing | None | N | 0.121 | neutral | None | None | None | None | N |
| N/F | 0.4825 | ambiguous | 0.499 | ambiguous | -0.732 | Destabilizing | 0.356 | N | 0.337 | neutral | None | None | None | None | N |
| N/G | 0.1635 | likely_benign | 0.1713 | benign | -0.163 | Destabilizing | 0.031 | N | 0.244 | neutral | None | None | None | None | N |
| N/H | 0.1166 | likely_benign | 0.1113 | benign | -0.226 | Destabilizing | None | N | 0.153 | neutral | N | 0.353448078 | None | None | N |
| N/I | 0.1913 | likely_benign | 0.1947 | benign | -0.014 | Destabilizing | 0.295 | N | 0.369 | neutral | N | 0.342150714 | None | None | N |
| N/K | 0.1462 | likely_benign | 0.1438 | benign | 0.087 | Stabilizing | None | N | 0.143 | neutral | N | 0.34000728 | None | None | N |
| N/L | 0.2039 | likely_benign | 0.2057 | benign | -0.014 | Destabilizing | 0.072 | N | 0.392 | neutral | None | None | None | None | N |
| N/M | 0.2948 | likely_benign | 0.3034 | benign | 0.106 | Stabilizing | 0.864 | D | 0.307 | neutral | None | None | None | None | N |
| N/P | 0.2146 | likely_benign | 0.2121 | benign | -0.02 | Destabilizing | 0.136 | N | 0.378 | neutral | None | None | None | None | N |
| N/Q | 0.1907 | likely_benign | 0.1935 | benign | -0.226 | Destabilizing | 0.038 | N | 0.195 | neutral | None | None | None | None | N |
| N/R | 0.1771 | likely_benign | 0.1746 | benign | 0.146 | Stabilizing | 0.038 | N | 0.199 | neutral | None | None | None | None | N |
| N/S | 0.0713 | likely_benign | 0.0676 | benign | None | Stabilizing | 0.012 | N | 0.289 | neutral | N | 0.330554468 | None | None | N |
| N/T | 0.1113 | likely_benign | 0.108 | benign | 0.028 | Stabilizing | 0.055 | N | 0.197 | neutral | N | 0.348112311 | None | None | N |
| N/V | 0.1819 | likely_benign | 0.1848 | benign | -0.02 | Destabilizing | 0.072 | N | 0.369 | neutral | None | None | None | None | N |
| N/W | 0.6365 | likely_pathogenic | 0.6351 | pathogenic | -0.889 | Destabilizing | 0.864 | D | 0.349 | neutral | None | None | None | None | N |
| N/Y | 0.1519 | likely_benign | 0.15 | benign | -0.561 | Destabilizing | 0.093 | N | 0.338 | neutral | N | 0.341868518 | 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.