Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27046 | 81361;81362;81363 | chr2:178564996;178564995;178564994 | chr2:179429723;179429722;179429721 |
| N2AB | 25405 | 76438;76439;76440 | chr2:178564996;178564995;178564994 | chr2:179429723;179429722;179429721 |
| N2A | 24478 | 73657;73658;73659 | chr2:178564996;178564995;178564994 | chr2:179429723;179429722;179429721 |
| N2B | 17981 | 54166;54167;54168 | chr2:178564996;178564995;178564994 | chr2:179429723;179429722;179429721 |
| Novex-1 | 18106 | 54541;54542;54543 | chr2:178564996;178564995;178564994 | chr2:179429723;179429722;179429721 |
| Novex-2 | 18173 | 54742;54743;54744 | chr2:178564996;178564995;178564994 | chr2:179429723;179429722;179429721 |
| 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/K | None | None | 0.014 | N | 0.328 | 0.239 | 0.241664281697 | gnomAD-4.0.0 | 6.84885E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9991E-07 | 0 | 0 |
| R/T | rs1705155978  |
None | 0.942 | N | 0.579 | 0.432 | 0.661190538856 | gnomAD-4.0.0 | 6.84885E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9991E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.979 | likely_pathogenic | 0.9844 | pathogenic | -2.122 | Highly Destabilizing | 0.754 | D | 0.583 | neutral | None | None | None | None | N |
| R/C | 0.6099 | likely_pathogenic | 0.6349 | pathogenic | -1.939 | Destabilizing | 0.998 | D | 0.75 | deleterious | None | None | None | None | N |
| R/D | 0.9977 | likely_pathogenic | 0.998 | pathogenic | -1.45 | Destabilizing | 0.956 | D | 0.659 | neutral | None | None | None | None | N |
| R/E | 0.9651 | likely_pathogenic | 0.9709 | pathogenic | -1.227 | Destabilizing | 0.754 | D | 0.579 | neutral | None | None | None | None | N |
| R/F | 0.9939 | likely_pathogenic | 0.9948 | pathogenic | -1.101 | Destabilizing | 0.993 | D | 0.762 | deleterious | None | None | None | None | N |
| R/G | 0.9675 | likely_pathogenic | 0.9734 | pathogenic | -2.434 | Highly Destabilizing | 0.822 | D | 0.629 | neutral | D | 0.554313325 | None | None | N |
| R/H | 0.4652 | ambiguous | 0.4524 | ambiguous | -2.177 | Highly Destabilizing | 0.978 | D | 0.603 | neutral | None | None | None | None | N |
| R/I | 0.9651 | likely_pathogenic | 0.9745 | pathogenic | -1.193 | Destabilizing | 0.971 | D | 0.753 | deleterious | D | 0.522384002 | None | None | N |
| R/K | 0.4142 | ambiguous | 0.4431 | ambiguous | -1.375 | Destabilizing | 0.014 | N | 0.328 | neutral | N | 0.498035096 | None | None | N |
| R/L | 0.9379 | likely_pathogenic | 0.9498 | pathogenic | -1.193 | Destabilizing | 0.86 | D | 0.629 | neutral | None | None | None | None | N |
| R/M | 0.9621 | likely_pathogenic | 0.9712 | pathogenic | -1.708 | Destabilizing | 0.998 | D | 0.644 | neutral | None | None | None | None | N |
| R/N | 0.988 | likely_pathogenic | 0.9891 | pathogenic | -1.675 | Destabilizing | 0.956 | D | 0.541 | neutral | None | None | None | None | N |
| R/P | 0.9991 | likely_pathogenic | 0.9993 | pathogenic | -1.497 | Destabilizing | 0.978 | D | 0.69 | prob.neutral | None | None | None | None | N |
| R/Q | 0.4285 | ambiguous | 0.4405 | ambiguous | -1.367 | Destabilizing | 0.915 | D | 0.552 | neutral | None | None | None | None | N |
| R/S | 0.9826 | likely_pathogenic | 0.9849 | pathogenic | -2.358 | Highly Destabilizing | 0.698 | D | 0.579 | neutral | D | 0.52830535 | None | None | N |
| R/T | 0.9743 | likely_pathogenic | 0.9815 | pathogenic | -1.943 | Destabilizing | 0.942 | D | 0.579 | neutral | N | 0.500263595 | None | None | N |
| R/V | 0.972 | likely_pathogenic | 0.9782 | pathogenic | -1.497 | Destabilizing | 0.956 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/W | 0.9121 | likely_pathogenic | 0.9238 | pathogenic | -0.748 | Destabilizing | 0.998 | D | 0.705 | prob.neutral | None | None | None | None | N |
| R/Y | 0.9771 | likely_pathogenic | 0.9774 | pathogenic | -0.693 | Destabilizing | 0.993 | D | 0.719 | prob.delet. | 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.