Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23415 | 70468;70469;70470 | chr2:178575889;178575888;178575887 | chr2:179440616;179440615;179440614 |
| N2AB | 21774 | 65545;65546;65547 | chr2:178575889;178575888;178575887 | chr2:179440616;179440615;179440614 |
| N2A | 20847 | 62764;62765;62766 | chr2:178575889;178575888;178575887 | chr2:179440616;179440615;179440614 |
| N2B | 14350 | 43273;43274;43275 | chr2:178575889;178575888;178575887 | chr2:179440616;179440615;179440614 |
| Novex-1 | 14475 | 43648;43649;43650 | chr2:178575889;178575888;178575887 | chr2:179440616;179440615;179440614 |
| Novex-2 | 14542 | 43849;43850;43851 | chr2:178575889;178575888;178575887 | chr2:179440616;179440615;179440614 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/L | rs200029470  |
-0.621 | 0.002 | N | 0.305 | 0.177 | 0.27479166964 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| M/L | rs200029470 |
-0.621 | 0.002 | N | 0.305 | 0.177 | 0.27479166964 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| M/L | rs200029470 |
-0.621 | 0.002 | N | 0.305 | 0.177 | 0.27479166964 | gnomAD-4.0.0 | 1.05354E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44115E-05 | 0 | 0 |
| M/T | rs765861604 |
-1.67 | 0.912 | N | 0.628 | 0.372 | 0.637519714765 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| M/T | rs765861604 |
-1.67 | 0.912 | N | 0.628 | 0.372 | 0.637519714765 | gnomAD-4.0.0 | 4.7749E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.5779E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.9201 | likely_pathogenic | 0.9294 | pathogenic | -2.25 | Highly Destabilizing | 0.85 | D | 0.602 | neutral | None | None | None | None | N |
| M/C | 0.868 | likely_pathogenic | 0.8788 | pathogenic | -1.966 | Destabilizing | 0.993 | D | 0.713 | prob.delet. | None | None | None | None | N |
| M/D | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -1.094 | Destabilizing | 0.993 | D | 0.729 | prob.delet. | None | None | None | None | N |
| M/E | 0.9959 | likely_pathogenic | 0.9965 | pathogenic | -0.921 | Destabilizing | 0.977 | D | 0.687 | prob.neutral | None | None | None | None | N |
| M/F | 0.7407 | likely_pathogenic | 0.7609 | pathogenic | -0.857 | Destabilizing | 0.872 | D | 0.592 | neutral | None | None | None | None | N |
| M/G | 0.9877 | likely_pathogenic | 0.9896 | pathogenic | -2.717 | Highly Destabilizing | 0.977 | D | 0.697 | prob.neutral | None | None | None | None | N |
| M/H | 0.9955 | likely_pathogenic | 0.9961 | pathogenic | -1.979 | Destabilizing | 0.998 | D | 0.741 | deleterious | None | None | None | None | N |
| M/I | 0.623 | likely_pathogenic | 0.6224 | pathogenic | -0.945 | Destabilizing | 0.028 | N | 0.327 | neutral | N | 0.354580042 | None | None | N |
| M/K | 0.9865 | likely_pathogenic | 0.9881 | pathogenic | -0.979 | Destabilizing | 0.969 | D | 0.631 | neutral | N | 0.465019958 | None | None | N |
| M/L | 0.1407 | likely_benign | 0.1412 | benign | -0.945 | Destabilizing | 0.002 | N | 0.305 | neutral | N | 0.299553479 | None | None | N |
| M/N | 0.9942 | likely_pathogenic | 0.995 | pathogenic | -1.166 | Destabilizing | 0.993 | D | 0.71 | prob.delet. | None | None | None | None | N |
| M/P | 0.9975 | likely_pathogenic | 0.9978 | pathogenic | -1.357 | Destabilizing | 0.993 | D | 0.708 | prob.delet. | None | None | None | None | N |
| M/Q | 0.978 | likely_pathogenic | 0.9812 | pathogenic | -0.97 | Destabilizing | 0.993 | D | 0.632 | neutral | None | None | None | None | N |
| M/R | 0.987 | likely_pathogenic | 0.9888 | pathogenic | -0.895 | Destabilizing | 0.969 | D | 0.7 | prob.neutral | N | 0.465019958 | None | None | N |
| M/S | 0.9842 | likely_pathogenic | 0.9865 | pathogenic | -1.895 | Destabilizing | 0.977 | D | 0.627 | neutral | None | None | None | None | N |
| M/T | 0.9334 | likely_pathogenic | 0.9406 | pathogenic | -1.577 | Destabilizing | 0.912 | D | 0.628 | neutral | N | 0.464673242 | None | None | N |
| M/V | 0.2023 | likely_benign | 0.2063 | benign | -1.357 | Destabilizing | 0.166 | N | 0.435 | neutral | N | 0.336378283 | None | None | N |
| M/W | 0.9918 | likely_pathogenic | 0.9924 | pathogenic | -0.951 | Destabilizing | 0.998 | D | 0.714 | prob.delet. | None | None | None | None | N |
| M/Y | 0.9805 | likely_pathogenic | 0.9822 | pathogenic | -0.977 | Destabilizing | 0.993 | D | 0.7 | 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.