Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3306 | 10141;10142;10143 | chr2:178764599;178764598;178764597 | chr2:179629326;179629325;179629324 |
| N2AB | 3306 | 10141;10142;10143 | chr2:178764599;178764598;178764597 | chr2:179629326;179629325;179629324 |
| N2A | 3306 | 10141;10142;10143 | chr2:178764599;178764598;178764597 | chr2:179629326;179629325;179629324 |
| N2B | 3260 | 10003;10004;10005 | chr2:178764599;178764598;178764597 | chr2:179629326;179629325;179629324 |
| Novex-1 | 3260 | 10003;10004;10005 | chr2:178764599;178764598;178764597 | chr2:179629326;179629325;179629324 |
| Novex-2 | 3260 | 10003;10004;10005 | chr2:178764599;178764598;178764597 | chr2:179629326;179629325;179629324 |
| Novex-3 | 3306 | 10141;10142;10143 | chr2:178764599;178764598;178764597 | chr2:179629326;179629325;179629324 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | None | None | 0.991 | D | 0.696 | 0.462 | 0.659281739986 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| A/V | rs879006488  |
-0.296 | 0.989 | D | 0.471 | 0.27 | 0.575180444326 | gnomAD-2.1.1 | 1.06E-05 | None | None | None | None | N | None | 4.01E-05 | 0 | None | 0 | 0 | None | 6.53E-05 | None | 0 | 0 | 0 |
| A/V | rs879006488 |
-0.296 | 0.989 | D | 0.471 | 0.27 | 0.575180444326 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 1.20755E-04 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07297E-04 | 0 |
| A/V | rs879006488 |
-0.296 | 0.989 | D | 0.471 | 0.27 | 0.575180444326 | gnomAD-4.0.0 | 9.9136E-06 | None | None | None | None | N | None | 9.34779E-05 | 1.66678E-05 | None | 0 | 0 | None | 0 | 0 | 5.08472E-06 | 2.19587E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.833 | likely_pathogenic | 0.8261 | pathogenic | -0.938 | Destabilizing | 0.999 | D | 0.579 | neutral | None | None | None | None | N |
| A/D | 0.6263 | likely_pathogenic | 0.6173 | pathogenic | -1.004 | Destabilizing | 0.91 | D | 0.623 | neutral | None | None | None | None | N |
| A/E | 0.3152 | likely_benign | 0.3661 | ambiguous | -1.069 | Destabilizing | 0.22 | N | 0.321 | neutral | N | 0.48702858 | None | None | N |
| A/F | 0.7561 | likely_pathogenic | 0.7652 | pathogenic | -1.118 | Destabilizing | 0.998 | D | 0.773 | deleterious | None | None | None | None | N |
| A/G | 0.2689 | likely_benign | 0.2437 | benign | -1.094 | Destabilizing | 0.951 | D | 0.443 | neutral | N | 0.509808083 | None | None | N |
| A/H | 0.7928 | likely_pathogenic | 0.8015 | pathogenic | -1.194 | Destabilizing | 0.998 | D | 0.74 | deleterious | None | None | None | None | N |
| A/I | 0.6161 | likely_pathogenic | 0.682 | pathogenic | -0.464 | Destabilizing | 0.993 | D | 0.702 | prob.neutral | None | None | None | None | N |
| A/K | 0.6693 | likely_pathogenic | 0.6939 | pathogenic | -1.125 | Destabilizing | 0.91 | D | 0.578 | neutral | None | None | None | None | N |
| A/L | 0.5215 | ambiguous | 0.5546 | ambiguous | -0.464 | Destabilizing | 0.953 | D | 0.577 | neutral | None | None | None | None | N |
| A/M | 0.4505 | ambiguous | 0.4878 | ambiguous | -0.375 | Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | N |
| A/N | 0.5548 | ambiguous | 0.5739 | pathogenic | -0.825 | Destabilizing | 0.986 | D | 0.719 | prob.delet. | None | None | None | None | N |
| A/P | 0.962 | likely_pathogenic | 0.9582 | pathogenic | -0.562 | Destabilizing | 0.991 | D | 0.696 | prob.neutral | D | 0.713171652 | None | None | N |
| A/Q | 0.4725 | ambiguous | 0.5106 | ambiguous | -1.033 | Destabilizing | 0.973 | D | 0.695 | prob.neutral | None | None | None | None | N |
| A/R | 0.5507 | ambiguous | 0.5636 | ambiguous | -0.723 | Destabilizing | 0.986 | D | 0.693 | prob.neutral | None | None | None | None | N |
| A/S | 0.1093 | likely_benign | 0.1244 | benign | -1.169 | Destabilizing | 0.17 | N | 0.261 | neutral | N | 0.468183511 | None | None | N |
| A/T | 0.1514 | likely_benign | 0.1965 | benign | -1.142 | Destabilizing | 0.885 | D | 0.453 | neutral | N | 0.512818854 | None | None | N |
| A/V | 0.3271 | likely_benign | 0.384 | ambiguous | -0.562 | Destabilizing | 0.989 | D | 0.471 | neutral | D | 0.548329372 | None | None | N |
| A/W | 0.9623 | likely_pathogenic | 0.961 | pathogenic | -1.386 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| A/Y | 0.8488 | likely_pathogenic | 0.8531 | pathogenic | -1.003 | Destabilizing | 0.998 | D | 0.764 | deleterious | 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.