Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32372 | 97339;97340;97341 | chr2:178542740;178542739;178542738 | chr2:179407467;179407466;179407465 |
| N2AB | 30731 | 92416;92417;92418 | chr2:178542740;178542739;178542738 | chr2:179407467;179407466;179407465 |
| N2A | 29804 | 89635;89636;89637 | chr2:178542740;178542739;178542738 | chr2:179407467;179407466;179407465 |
| N2B | 23307 | 70144;70145;70146 | chr2:178542740;178542739;178542738 | chr2:179407467;179407466;179407465 |
| Novex-1 | 23432 | 70519;70520;70521 | chr2:178542740;178542739;178542738 | chr2:179407467;179407466;179407465 |
| Novex-2 | 23499 | 70720;70721;70722 | chr2:178542740;178542739;178542738 | chr2:179407467;179407466;179407465 |
| 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 | rs1298215224  |
-0.437 | 0.024 | N | 0.215 | 0.076 | 0.254761474806 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14732E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs1298215224 |
-0.437 | 0.024 | N | 0.215 | 0.076 | 0.254761474806 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/G | rs1298215224 |
-0.437 | 0.024 | N | 0.215 | 0.076 | 0.254761474806 | gnomAD-4.0.0 | 5.07563E-06 | None | None | None | None | I | None | 1.74697E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.82083E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.1702 | likely_benign | 0.1649 | benign | 0.053 | Stabilizing | 0.007 | N | 0.225 | neutral | None | None | None | None | I |
| R/C | 0.1534 | likely_benign | 0.1234 | benign | -0.192 | Destabilizing | 0.864 | D | 0.245 | neutral | None | None | None | None | I |
| R/D | 0.3188 | likely_benign | 0.28 | benign | -0.273 | Destabilizing | None | N | 0.111 | neutral | None | None | None | None | I |
| R/E | 0.1975 | likely_benign | 0.1821 | benign | -0.236 | Destabilizing | None | N | 0.125 | neutral | None | None | None | None | I |
| R/F | 0.3852 | ambiguous | 0.312 | benign | -0.286 | Destabilizing | 0.356 | N | 0.32 | neutral | None | None | None | None | I |
| R/G | 0.1299 | likely_benign | 0.1131 | benign | -0.081 | Destabilizing | 0.024 | N | 0.215 | neutral | N | 0.456515118 | None | None | I |
| R/H | 0.0805 | likely_benign | 0.0693 | benign | -0.606 | Destabilizing | None | N | 0.149 | neutral | None | None | None | None | I |
| R/I | 0.224 | likely_benign | 0.2056 | benign | 0.36 | Stabilizing | 0.106 | N | 0.361 | neutral | N | 0.487531458 | None | None | I |
| R/K | 0.0818 | likely_benign | 0.0868 | benign | -0.12 | Destabilizing | None | N | 0.122 | neutral | N | 0.434793052 | None | None | I |
| R/L | 0.1522 | likely_benign | 0.1303 | benign | 0.36 | Stabilizing | 0.031 | N | 0.255 | neutral | None | None | None | None | I |
| R/M | 0.1968 | likely_benign | 0.1929 | benign | -0.049 | Destabilizing | 0.628 | D | 0.271 | neutral | None | None | None | None | I |
| R/N | 0.2448 | likely_benign | 0.2212 | benign | -0.012 | Destabilizing | None | N | 0.099 | neutral | None | None | None | None | I |
| R/P | 0.5275 | ambiguous | 0.4556 | ambiguous | 0.276 | Stabilizing | 0.136 | N | 0.383 | neutral | None | None | None | None | I |
| R/Q | 0.0771 | likely_benign | 0.0737 | benign | -0.054 | Destabilizing | 0.016 | N | 0.238 | neutral | None | None | None | None | I |
| R/S | 0.2096 | likely_benign | 0.1887 | benign | -0.19 | Destabilizing | 0.005 | N | 0.225 | neutral | N | 0.405699509 | None | None | I |
| R/T | 0.1257 | likely_benign | 0.1228 | benign | -0.049 | Destabilizing | 0.024 | N | 0.266 | neutral | N | 0.436755921 | None | None | I |
| R/V | 0.2428 | likely_benign | 0.2229 | benign | 0.276 | Stabilizing | 0.072 | N | 0.361 | neutral | None | None | None | None | I |
| R/W | 0.171 | likely_benign | 0.1345 | benign | -0.48 | Destabilizing | 0.864 | D | 0.265 | neutral | None | None | None | None | I |
| R/Y | 0.2477 | likely_benign | 0.193 | benign | -0.068 | Destabilizing | 0.072 | N | 0.391 | neutral | None | None | 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.