Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17903 | 53932;53933;53934 | chr2:178605588;178605587;178605586 | chr2:179470315;179470314;179470313 |
| N2AB | 16262 | 49009;49010;49011 | chr2:178605588;178605587;178605586 | chr2:179470315;179470314;179470313 |
| N2A | 15335 | 46228;46229;46230 | chr2:178605588;178605587;178605586 | chr2:179470315;179470314;179470313 |
| N2B | 8838 | 26737;26738;26739 | chr2:178605588;178605587;178605586 | chr2:179470315;179470314;179470313 |
| Novex-1 | 8963 | 27112;27113;27114 | chr2:178605588;178605587;178605586 | chr2:179470315;179470314;179470313 |
| Novex-2 | 9030 | 27313;27314;27315 | chr2:178605588;178605587;178605586 | chr2:179470315;179470314;179470313 |
| 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/C | rs1016726284  |
-0.993 | 1.0 | N | 0.703 | 0.359 | 0.568250393081 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.78E-05 | 0 |
| R/C | rs1016726284 |
-0.993 | 1.0 | N | 0.703 | 0.359 | 0.568250393081 | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs1016726284 |
-0.993 | 1.0 | N | 0.703 | 0.359 | 0.568250393081 | gnomAD-4.0.0 | 9.92555E-06 | None | None | None | None | N | None | 2.67566E-05 | 0 | None | 0 | 4.46887E-05 | None | 0 | 0 | 5.93851E-06 | 3.29815E-05 | 3.20657E-05 |
| R/G | rs1016726284 |
None | 0.036 | N | 0.321 | 0.179 | 0.386395597597 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07555E-04 | 0 |
| R/G | rs1016726284 |
None | 0.036 | N | 0.321 | 0.179 | 0.386395597597 | gnomAD-4.0.0 | 6.58657E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07555E-04 | 0 |
| R/H | rs755252821 |
-1.978 | 0.998 | N | 0.561 | 0.321 | None | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.84E-06 | 0 |
| R/H | rs755252821 |
-1.978 | 0.998 | N | 0.561 | 0.321 | None | gnomAD-3.1.2 | 6.6E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs755252821 |
-1.978 | 0.998 | N | 0.561 | 0.321 | None | gnomAD-4.0.0 | 1.67614E-05 | None | None | None | None | N | None | 1.33758E-05 | 1.67023E-05 | None | 0 | 0 | None | 0 | 0 | 1.95221E-05 | 2.20124E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5481 | ambiguous | 0.4702 | ambiguous | -0.936 | Destabilizing | 0.754 | D | 0.462 | neutral | None | None | None | None | N |
| R/C | 0.1751 | likely_benign | 0.1683 | benign | -0.731 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.497626568 | None | None | N |
| R/D | 0.9114 | likely_pathogenic | 0.8676 | pathogenic | -0.169 | Destabilizing | 0.956 | D | 0.585 | neutral | None | None | None | None | N |
| R/E | 0.6163 | likely_pathogenic | 0.5453 | ambiguous | 0.006 | Stabilizing | 0.926 | D | 0.505 | neutral | None | None | None | None | N |
| R/F | 0.7263 | likely_pathogenic | 0.6885 | pathogenic | -0.404 | Destabilizing | 0.993 | D | 0.705 | prob.neutral | None | None | None | None | N |
| R/G | 0.5072 | ambiguous | 0.43 | ambiguous | -1.309 | Destabilizing | 0.036 | N | 0.321 | neutral | N | 0.49177499 | None | None | N |
| R/H | 0.1897 | likely_benign | 0.1626 | benign | -1.644 | Destabilizing | 0.998 | D | 0.561 | neutral | N | 0.473899999 | None | None | N |
| R/I | 0.4351 | ambiguous | 0.3693 | ambiguous | 0.095 | Stabilizing | 0.993 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/K | 0.1297 | likely_benign | 0.1185 | benign | -0.871 | Destabilizing | 0.717 | D | 0.435 | neutral | None | None | None | None | N |
| R/L | 0.2933 | likely_benign | 0.2502 | benign | 0.095 | Stabilizing | 0.988 | D | 0.543 | neutral | N | 0.490428196 | None | None | N |
| R/M | 0.4265 | ambiguous | 0.3566 | ambiguous | -0.323 | Destabilizing | 0.998 | D | 0.625 | neutral | None | None | None | None | N |
| R/N | 0.8154 | likely_pathogenic | 0.7344 | pathogenic | -0.475 | Destabilizing | 0.956 | D | 0.517 | neutral | None | None | None | None | N |
| R/P | 0.5648 | likely_pathogenic | 0.4575 | ambiguous | -0.229 | Destabilizing | 0.996 | D | 0.677 | prob.neutral | N | 0.474437236 | None | None | N |
| R/Q | 0.1346 | likely_benign | 0.1203 | benign | -0.467 | Destabilizing | 0.993 | D | 0.543 | neutral | None | None | None | None | N |
| R/S | 0.7443 | likely_pathogenic | 0.6745 | pathogenic | -1.205 | Destabilizing | 0.922 | D | 0.551 | neutral | N | 0.471359645 | None | None | N |
| R/T | 0.5642 | likely_pathogenic | 0.4537 | ambiguous | -0.823 | Destabilizing | 0.978 | D | 0.548 | neutral | None | None | None | None | N |
| R/V | 0.5147 | ambiguous | 0.4492 | ambiguous | -0.229 | Destabilizing | 0.978 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/W | 0.324 | likely_benign | 0.3126 | benign | -0.02 | Destabilizing | 0.998 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/Y | 0.5967 | likely_pathogenic | 0.5622 | ambiguous | 0.207 | Stabilizing | 0.993 | D | 0.686 | prob.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.