Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32978 | 99157;99158;99159 | chr2:178539003;178539002;178539001 | chr2:179403730;179403729;179403728 |
| N2AB | 31337 | 94234;94235;94236 | chr2:178539003;178539002;178539001 | chr2:179403730;179403729;179403728 |
| N2A | 30410 | 91453;91454;91455 | chr2:178539003;178539002;178539001 | chr2:179403730;179403729;179403728 |
| N2B | 23913 | 71962;71963;71964 | chr2:178539003;178539002;178539001 | chr2:179403730;179403729;179403728 |
| Novex-1 | 24038 | 72337;72338;72339 | chr2:178539003;178539002;178539001 | chr2:179403730;179403729;179403728 |
| Novex-2 | 24105 | 72538;72539;72540 | chr2:178539003;178539002;178539001 | chr2:179403730;179403729;179403728 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1190695147  |
None | 0.78 | N | 0.371 | 0.237 | 0.366659145958 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs1190695147 |
None | 0.78 | N | 0.371 | 0.237 | 0.366659145958 | gnomAD-4.0.0 | 3.71836E-06 | None | None | None | None | I | None | 0 | 1.667E-05 | None | 0 | 0 | None | 0 | 0 | 4.23836E-06 | 0 | 0 |
| V/D | None | None | 0.995 | N | 0.713 | 0.428 | 0.741985612866 | gnomAD-4.0.0 | 3.42129E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.4977E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2629 | likely_benign | 0.3049 | benign | -0.391 | Destabilizing | 0.78 | D | 0.371 | neutral | N | 0.388455834 | None | None | I |
| V/C | 0.8366 | likely_pathogenic | 0.8388 | pathogenic | -0.635 | Destabilizing | 0.999 | D | 0.527 | neutral | None | None | None | None | I |
| V/D | 0.8743 | likely_pathogenic | 0.9128 | pathogenic | -0.229 | Destabilizing | 0.995 | D | 0.713 | prob.delet. | N | 0.506128367 | None | None | I |
| V/E | 0.7782 | likely_pathogenic | 0.8241 | pathogenic | -0.358 | Destabilizing | 0.996 | D | 0.689 | prob.neutral | None | None | None | None | I |
| V/F | 0.4007 | ambiguous | 0.43 | ambiguous | -0.717 | Destabilizing | 0.968 | D | 0.515 | neutral | N | 0.472671941 | None | None | I |
| V/G | 0.5899 | likely_pathogenic | 0.6387 | pathogenic | -0.491 | Destabilizing | 0.995 | D | 0.677 | prob.neutral | N | 0.491524274 | None | None | I |
| V/H | 0.8928 | likely_pathogenic | 0.9096 | pathogenic | -0.036 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | I |
| V/I | 0.0865 | likely_benign | 0.086 | benign | -0.285 | Destabilizing | 0.004 | N | 0.173 | neutral | N | 0.380319141 | None | None | I |
| V/K | 0.808 | likely_pathogenic | 0.8348 | pathogenic | -0.258 | Destabilizing | 0.988 | D | 0.693 | prob.neutral | None | None | None | None | I |
| V/L | 0.4171 | ambiguous | 0.4932 | ambiguous | -0.285 | Destabilizing | 0.437 | N | 0.267 | neutral | N | 0.451680594 | None | None | I |
| V/M | 0.3118 | likely_benign | 0.3655 | ambiguous | -0.29 | Destabilizing | 0.976 | D | 0.457 | neutral | None | None | None | None | I |
| V/N | 0.7024 | likely_pathogenic | 0.7726 | pathogenic | -0.039 | Destabilizing | 0.996 | D | 0.706 | prob.neutral | None | None | None | None | I |
| V/P | 0.9721 | likely_pathogenic | 0.9773 | pathogenic | -0.287 | Destabilizing | 0.996 | D | 0.703 | prob.neutral | None | None | None | None | I |
| V/Q | 0.7514 | likely_pathogenic | 0.7985 | pathogenic | -0.322 | Destabilizing | 0.996 | D | 0.701 | prob.neutral | None | None | None | None | I |
| V/R | 0.6979 | likely_pathogenic | 0.7249 | pathogenic | 0.278 | Stabilizing | 0.996 | D | 0.711 | prob.delet. | None | None | None | None | I |
| V/S | 0.4569 | ambiguous | 0.53 | ambiguous | -0.399 | Destabilizing | 0.988 | D | 0.651 | neutral | None | None | None | None | I |
| V/T | 0.2929 | likely_benign | 0.3652 | ambiguous | -0.429 | Destabilizing | 0.919 | D | 0.374 | neutral | None | None | None | None | I |
| V/W | 0.9579 | likely_pathogenic | 0.9597 | pathogenic | -0.758 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | I |
| V/Y | 0.8448 | likely_pathogenic | 0.8613 | pathogenic | -0.447 | Destabilizing | 0.996 | D | 0.536 | 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.