Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23968 | 72127;72128;72129 | chr2:178574230;178574229;178574228 | chr2:179438957;179438956;179438955 |
| N2AB | 22327 | 67204;67205;67206 | chr2:178574230;178574229;178574228 | chr2:179438957;179438956;179438955 |
| N2A | 21400 | 64423;64424;64425 | chr2:178574230;178574229;178574228 | chr2:179438957;179438956;179438955 |
| N2B | 14903 | 44932;44933;44934 | chr2:178574230;178574229;178574228 | chr2:179438957;179438956;179438955 |
| Novex-1 | 15028 | 45307;45308;45309 | chr2:178574230;178574229;178574228 | chr2:179438957;179438956;179438955 |
| Novex-2 | 15095 | 45508;45509;45510 | chr2:178574230;178574229;178574228 | chr2:179438957;179438956;179438955 |
| 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/T | rs769320596  |
0.166 | 0.012 | N | 0.282 | 0.069 | 0.203808441222 | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 0 | 0 | None | 1.99362E-04 | 0 | None | 0 | None | 0 | 1.79E-05 | 1.66113E-04 |
| N/T | rs769320596 |
0.166 | 0.012 | N | 0.282 | 0.069 | 0.203808441222 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 8.64553E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/T | rs769320596 |
0.166 | 0.012 | N | 0.282 | 0.069 | 0.203808441222 | gnomAD-4.0.0 | 2.6655E-05 | None | None | None | None | N | None | 0 | 0 | None | 8.1114E-04 | 0 | None | 1.5623E-05 | 0 | 1.18693E-05 | 0 | 6.40594E-05 |
| N/Y | None | None | 0.093 | N | 0.409 | 0.175 | 0.359357374593 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 | 0.1148 | likely_benign | 0.1479 | benign | -0.053 | Destabilizing | None | N | 0.188 | neutral | None | None | None | None | N |
| N/C | 0.2166 | likely_benign | 0.2649 | benign | 0.057 | Stabilizing | 0.864 | D | 0.402 | neutral | None | None | None | None | N |
| N/D | 0.0855 | likely_benign | 0.0981 | benign | 0.022 | Stabilizing | None | N | 0.111 | neutral | N | 0.391706783 | None | None | N |
| N/E | 0.2002 | likely_benign | 0.2495 | benign | -0.043 | Destabilizing | 0.016 | N | 0.327 | neutral | None | None | None | None | N |
| N/F | 0.3616 | ambiguous | 0.4677 | ambiguous | -0.697 | Destabilizing | 0.214 | N | 0.441 | neutral | None | None | None | None | N |
| N/G | 0.1396 | likely_benign | 0.1767 | benign | -0.128 | Destabilizing | 0.016 | N | 0.26 | neutral | None | None | None | None | N |
| N/H | 0.0882 | likely_benign | 0.1054 | benign | -0.14 | Destabilizing | None | N | 0.179 | neutral | N | 0.504242855 | None | None | N |
| N/I | 0.201 | likely_benign | 0.2631 | benign | 0.043 | Stabilizing | 0.295 | N | 0.451 | neutral | D | 0.523695407 | None | None | N |
| N/K | 0.1846 | likely_benign | 0.2289 | benign | 0.049 | Stabilizing | 0.029 | N | 0.267 | neutral | N | 0.474034591 | None | None | N |
| N/L | 0.1849 | likely_benign | 0.2277 | benign | 0.043 | Stabilizing | 0.072 | N | 0.353 | neutral | None | None | None | None | N |
| N/M | 0.2593 | likely_benign | 0.3134 | benign | 0.024 | Stabilizing | 0.864 | D | 0.365 | neutral | None | None | None | None | N |
| N/P | 0.4855 | ambiguous | 0.6082 | pathogenic | 0.033 | Stabilizing | 0.356 | N | 0.427 | neutral | None | None | None | None | N |
| N/Q | 0.1897 | likely_benign | 0.2295 | benign | -0.292 | Destabilizing | 0.072 | N | 0.32 | neutral | None | None | None | None | N |
| N/R | 0.2184 | likely_benign | 0.2866 | benign | 0.122 | Stabilizing | 0.072 | N | 0.299 | neutral | None | None | None | None | N |
| N/S | 0.0619 | likely_benign | 0.0654 | benign | -0.074 | Destabilizing | None | N | 0.099 | neutral | N | 0.398459397 | None | None | N |
| N/T | 0.0974 | likely_benign | 0.1103 | benign | -0.037 | Destabilizing | 0.012 | N | 0.282 | neutral | N | 0.450504371 | None | None | N |
| N/V | 0.1724 | likely_benign | 0.2214 | benign | 0.033 | Stabilizing | 0.072 | N | 0.403 | neutral | None | None | None | None | N |
| N/W | 0.6298 | likely_pathogenic | 0.7243 | pathogenic | -0.867 | Destabilizing | 0.864 | D | 0.457 | neutral | None | None | None | None | N |
| N/Y | 0.1396 | likely_benign | 0.171 | benign | -0.529 | Destabilizing | 0.093 | N | 0.409 | neutral | N | 0.518846948 | 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.