Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14702 | 44329;44330;44331 | chr2:178630854;178630853;178630852 | chr2:179495581;179495580;179495579 |
| N2AB | 13061 | 39406;39407;39408 | chr2:178630854;178630853;178630852 | chr2:179495581;179495580;179495579 |
| N2A | 12134 | 36625;36626;36627 | chr2:178630854;178630853;178630852 | chr2:179495581;179495580;179495579 |
| N2B | 5637 | 17134;17135;17136 | chr2:178630854;178630853;178630852 | chr2:179495581;179495580;179495579 |
| Novex-1 | 5762 | 17509;17510;17511 | chr2:178630854;178630853;178630852 | chr2:179495581;179495580;179495579 |
| Novex-2 | 5829 | 17710;17711;17712 | chr2:178630854;178630853;178630852 | chr2:179495581;179495580;179495579 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | rs727503627  |
0.366 | 0.999 | D | 0.793 | 0.409 | 0.251639045875 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.3077E-04 | None | 0 | 0 | 0 |
| D/H | rs727503627 |
0.366 | 0.999 | D | 0.793 | 0.409 | 0.251639045875 | gnomAD-4.0.0 | 9.5535E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 8.59919E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2358 | likely_benign | 0.3238 | benign | -0.024 | Destabilizing | 0.908 | D | 0.677 | prob.neutral | D | 0.522588403 | None | None | N |
| D/C | 0.6346 | likely_pathogenic | 0.7802 | pathogenic | -0.113 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| D/E | 0.2641 | likely_benign | 0.2852 | benign | -0.158 | Destabilizing | 0.976 | D | 0.51 | neutral | N | 0.415367365 | None | None | N |
| D/F | 0.622 | likely_pathogenic | 0.7488 | pathogenic | -0.105 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| D/G | 0.1242 | likely_benign | 0.2016 | benign | -0.158 | Destabilizing | 0.058 | N | 0.421 | neutral | N | 0.433820055 | None | None | N |
| D/H | 0.3079 | likely_benign | 0.4341 | ambiguous | 0.398 | Stabilizing | 0.999 | D | 0.793 | deleterious | D | 0.566868761 | None | None | N |
| D/I | 0.458 | ambiguous | 0.5901 | pathogenic | 0.265 | Stabilizing | 0.998 | D | 0.809 | deleterious | None | None | None | None | N |
| D/K | 0.3803 | ambiguous | 0.5629 | ambiguous | 0.304 | Stabilizing | 0.995 | D | 0.773 | deleterious | None | None | None | None | N |
| D/L | 0.4845 | ambiguous | 0.6315 | pathogenic | 0.265 | Stabilizing | 0.995 | D | 0.734 | deleterious | None | None | None | None | N |
| D/M | 0.6995 | likely_pathogenic | 0.8072 | pathogenic | 0.085 | Stabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| D/N | 0.0999 | likely_benign | 0.1249 | benign | 0.205 | Stabilizing | 0.986 | D | 0.796 | deleterious | N | 0.44880691 | None | None | N |
| D/P | 0.8425 | likely_pathogenic | 0.8969 | pathogenic | 0.189 | Stabilizing | 0.998 | D | 0.74 | deleterious | None | None | None | None | N |
| D/Q | 0.4368 | ambiguous | 0.5799 | pathogenic | 0.209 | Stabilizing | 0.998 | D | 0.735 | deleterious | None | None | None | None | N |
| D/R | 0.4083 | ambiguous | 0.576 | pathogenic | 0.556 | Stabilizing | 0.995 | D | 0.792 | deleterious | None | None | None | None | N |
| D/S | 0.1462 | likely_benign | 0.1998 | benign | 0.05 | Stabilizing | 0.963 | D | 0.729 | deleterious | None | None | None | None | N |
| D/T | 0.3038 | likely_benign | 0.3852 | ambiguous | 0.153 | Stabilizing | 0.995 | D | 0.777 | deleterious | None | None | None | None | N |
| D/V | 0.3264 | likely_benign | 0.4282 | ambiguous | 0.189 | Stabilizing | 0.993 | D | 0.731 | deleterious | N | 0.485014366 | None | None | N |
| D/W | 0.8924 | likely_pathogenic | 0.9463 | pathogenic | -0.062 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| D/Y | 0.2485 | likely_benign | 0.3611 | ambiguous | 0.116 | Stabilizing | 0.999 | D | 0.791 | deleterious | D | 0.526922329 | 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.