Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35014 | 105265;105266;105267 | chr2:178531575;178531574;178531573 | chr2:179396302;179396301;179396300 |
| N2AB | 33373 | 100342;100343;100344 | chr2:178531575;178531574;178531573 | chr2:179396302;179396301;179396300 |
| N2A | 32446 | 97561;97562;97563 | chr2:178531575;178531574;178531573 | chr2:179396302;179396301;179396300 |
| N2B | 25949 | 78070;78071;78072 | chr2:178531575;178531574;178531573 | chr2:179396302;179396301;179396300 |
| Novex-1 | 26074 | 78445;78446;78447 | chr2:178531575;178531574;178531573 | chr2:179396302;179396301;179396300 |
| Novex-2 | 26141 | 78646;78647;78648 | chr2:178531575;178531574;178531573 | chr2:179396302;179396301;179396300 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | rs758356886  |
-2.575 | 0.995 | N | 0.801 | 0.287 | 0.485634191555 | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 1.99872E-04 | 1.56E-05 | 0 |
| A/D | rs758356886 |
-2.575 | 0.995 | N | 0.801 | 0.287 | 0.485634191555 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 0 | 0 | 0 |
| A/D | rs758356886 |
-2.575 | 0.995 | N | 0.801 | 0.287 | 0.485634191555 | gnomAD-4.0.0 | 1.11533E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.5623E-04 | 0 | 2.5426E-06 | 0 | 8.00487E-05 |
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 | 0.7715 | likely_pathogenic | 0.8029 | pathogenic | -0.985 | Destabilizing | 0.034 | N | 0.455 | neutral | None | None | None | None | N |
| A/D | 0.9972 | likely_pathogenic | 0.9984 | pathogenic | -2.378 | Highly Destabilizing | 0.995 | D | 0.801 | deleterious | N | 0.456426129 | None | None | N |
| A/E | 0.9927 | likely_pathogenic | 0.9957 | pathogenic | -2.135 | Highly Destabilizing | 0.988 | D | 0.75 | deleterious | None | None | None | None | N |
| A/F | 0.9632 | likely_pathogenic | 0.9755 | pathogenic | -0.565 | Destabilizing | 0.976 | D | 0.812 | deleterious | None | None | None | None | N |
| A/G | 0.5255 | ambiguous | 0.5728 | pathogenic | -1.515 | Destabilizing | 0.946 | D | 0.714 | prob.delet. | N | 0.456426129 | None | None | N |
| A/H | 0.9972 | likely_pathogenic | 0.998 | pathogenic | -2.111 | Highly Destabilizing | 0.999 | D | 0.821 | deleterious | None | None | None | None | N |
| A/I | 0.6402 | likely_pathogenic | 0.8005 | pathogenic | 0.457 | Stabilizing | 0.851 | D | 0.705 | prob.neutral | None | None | None | None | N |
| A/K | 0.9984 | likely_pathogenic | 0.999 | pathogenic | -1.075 | Destabilizing | 0.988 | D | 0.749 | deleterious | None | None | None | None | N |
| A/L | 0.6067 | likely_pathogenic | 0.7047 | pathogenic | 0.457 | Stabilizing | 0.702 | D | 0.704 | prob.neutral | None | None | None | None | N |
| A/M | 0.7528 | likely_pathogenic | 0.8432 | pathogenic | 0.158 | Stabilizing | 0.988 | D | 0.77 | deleterious | None | None | None | None | N |
| A/N | 0.9891 | likely_pathogenic | 0.9932 | pathogenic | -1.482 | Destabilizing | 0.996 | D | 0.815 | deleterious | None | None | None | None | N |
| A/P | 0.9915 | likely_pathogenic | 0.9957 | pathogenic | 0.019 | Stabilizing | 0.995 | D | 0.763 | deleterious | N | 0.456426129 | None | None | N |
| A/Q | 0.9889 | likely_pathogenic | 0.992 | pathogenic | -1.197 | Destabilizing | 0.996 | D | 0.755 | deleterious | None | None | None | None | N |
| A/R | 0.994 | likely_pathogenic | 0.9953 | pathogenic | -1.32 | Destabilizing | 0.988 | D | 0.755 | deleterious | None | None | None | None | N |
| A/S | 0.5129 | ambiguous | 0.5811 | pathogenic | -1.885 | Destabilizing | 0.946 | D | 0.709 | prob.delet. | N | 0.456426129 | None | None | N |
| A/T | 0.5083 | ambiguous | 0.6611 | pathogenic | -1.503 | Destabilizing | 0.896 | D | 0.713 | prob.delet. | N | 0.45617264 | None | None | N |
| A/V | 0.237 | likely_benign | 0.3794 | ambiguous | 0.019 | Stabilizing | 0.011 | N | 0.425 | neutral | N | 0.39956297 | None | None | N |
| A/W | 0.9986 | likely_pathogenic | 0.9991 | pathogenic | -1.461 | Destabilizing | 0.999 | D | 0.834 | deleterious | None | None | None | None | N |
| A/Y | 0.9928 | likely_pathogenic | 0.9951 | pathogenic | -0.84 | Destabilizing | 0.988 | D | 0.821 | 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.