Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19249 | 57970;57971;57972 | chr2:178595609;178595608;178595607 | chr2:179460336;179460335;179460334 |
| N2AB | 17608 | 53047;53048;53049 | chr2:178595609;178595608;178595607 | chr2:179460336;179460335;179460334 |
| N2A | 16681 | 50266;50267;50268 | chr2:178595609;178595608;178595607 | chr2:179460336;179460335;179460334 |
| N2B | 10184 | 30775;30776;30777 | chr2:178595609;178595608;178595607 | chr2:179460336;179460335;179460334 |
| Novex-1 | 10309 | 31150;31151;31152 | chr2:178595609;178595608;178595607 | chr2:179460336;179460335;179460334 |
| Novex-2 | 10376 | 31351;31352;31353 | chr2:178595609;178595608;178595607 | chr2:179460336;179460335;179460334 |
| 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/T | rs2051354883  |
None | 0.051 | N | 0.182 | 0.172 | 0.451407941134 | gnomAD-4.0.0 | 1.63883E-06 | None | None | None | None | N | None | 0 | 2.43072E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | None | None | 0.454 | N | 0.304 | 0.092 | 0.399449838166 | gnomAD-4.0.0 | 3.2748E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.93701E-06 | 1.49799E-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 | 0.2401 | likely_benign | 0.3236 | benign | -1.452 | Destabilizing | 0.525 | D | 0.36 | neutral | None | None | None | None | N |
| I/C | 0.4817 | ambiguous | 0.5812 | pathogenic | -1.036 | Destabilizing | 0.998 | D | 0.406 | neutral | None | None | None | None | N |
| I/D | 0.4873 | ambiguous | 0.6594 | pathogenic | -0.71 | Destabilizing | 0.904 | D | 0.422 | neutral | None | None | None | None | N |
| I/E | 0.3287 | likely_benign | 0.4877 | ambiguous | -0.67 | Destabilizing | 0.949 | D | 0.417 | neutral | None | None | None | None | N |
| I/F | 0.1265 | likely_benign | 0.1841 | benign | -0.843 | Destabilizing | 0.934 | D | 0.407 | neutral | N | 0.505050932 | None | None | N |
| I/G | 0.4395 | ambiguous | 0.5683 | pathogenic | -1.789 | Destabilizing | 0.842 | D | 0.38 | neutral | None | None | None | None | N |
| I/H | 0.2646 | likely_benign | 0.4139 | ambiguous | -0.791 | Destabilizing | 0.993 | D | 0.417 | neutral | None | None | None | None | N |
| I/K | 0.2533 | likely_benign | 0.4242 | ambiguous | -0.989 | Destabilizing | 0.949 | D | 0.408 | neutral | None | None | None | None | N |
| I/L | 0.0761 | likely_benign | 0.0865 | benign | -0.593 | Destabilizing | 0.005 | N | 0.074 | neutral | N | 0.464703032 | None | None | N |
| I/M | 0.0912 | likely_benign | 0.1023 | benign | -0.643 | Destabilizing | 0.934 | D | 0.424 | neutral | N | 0.502087984 | None | None | N |
| I/N | 0.1469 | likely_benign | 0.2315 | benign | -0.95 | Destabilizing | 0.111 | N | 0.331 | neutral | N | 0.477613614 | None | None | N |
| I/P | 0.6677 | likely_pathogenic | 0.8066 | pathogenic | -0.848 | Destabilizing | 0.974 | D | 0.453 | neutral | None | None | None | None | N |
| I/Q | 0.2036 | likely_benign | 0.3056 | benign | -1.035 | Destabilizing | 0.974 | D | 0.447 | neutral | None | None | None | None | N |
| I/R | 0.1981 | likely_benign | 0.3651 | ambiguous | -0.456 | Destabilizing | 0.974 | D | 0.441 | neutral | None | None | None | None | N |
| I/S | 0.1625 | likely_benign | 0.2438 | benign | -1.598 | Destabilizing | 0.669 | D | 0.358 | neutral | N | 0.464068314 | None | None | N |
| I/T | 0.1388 | likely_benign | 0.2027 | benign | -1.427 | Destabilizing | 0.051 | N | 0.182 | neutral | N | 0.429262307 | None | None | N |
| I/V | 0.0847 | likely_benign | 0.0882 | benign | -0.848 | Destabilizing | 0.454 | N | 0.304 | neutral | N | 0.438383222 | None | None | N |
| I/W | 0.6232 | likely_pathogenic | 0.7554 | pathogenic | -0.902 | Destabilizing | 0.998 | D | 0.525 | neutral | None | None | None | None | N |
| I/Y | 0.345 | ambiguous | 0.4889 | ambiguous | -0.676 | Destabilizing | 0.991 | D | 0.427 | neutral | 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.