Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31985 | 96178;96179;96180 | chr2:178544276;178544275;178544274 | chr2:179409003;179409002;179409001 |
| N2AB | 30344 | 91255;91256;91257 | chr2:178544276;178544275;178544274 | chr2:179409003;179409002;179409001 |
| N2A | 29417 | 88474;88475;88476 | chr2:178544276;178544275;178544274 | chr2:179409003;179409002;179409001 |
| N2B | 22920 | 68983;68984;68985 | chr2:178544276;178544275;178544274 | chr2:179409003;179409002;179409001 |
| Novex-1 | 23045 | 69358;69359;69360 | chr2:178544276;178544275;178544274 | chr2:179409003;179409002;179409001 |
| Novex-2 | 23112 | 69559;69560;69561 | chr2:178544276;178544275;178544274 | chr2:179409003;179409002;179409001 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/D | rs1242003251  |
-3.324 | 1.0 | D | 0.907 | 0.802 | 0.914900559549 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| V/D | rs1242003251 |
-3.324 | 1.0 | D | 0.907 | 0.802 | 0.914900559549 | gnomAD-4.0.0 | 1.59135E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02425E-05 |
| V/I | rs373484878 |
-0.743 | 0.997 | D | 0.624 | 0.402 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs373484878 |
-0.743 | 0.997 | D | 0.624 | 0.402 | None | gnomAD-4.0.0 | 4.05982E-06 | None | None | None | None | N | None | 6.9891E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6521 | likely_pathogenic | 0.6603 | pathogenic | -2.718 | Highly Destabilizing | 0.999 | D | 0.658 | neutral | D | 0.537337701 | None | None | N |
| V/C | 0.939 | likely_pathogenic | 0.9461 | pathogenic | -1.941 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| V/D | 0.9977 | likely_pathogenic | 0.9975 | pathogenic | -3.322 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | D | 0.635055617 | None | None | N |
| V/E | 0.9924 | likely_pathogenic | 0.992 | pathogenic | -3.019 | Highly Destabilizing | 1.0 | D | 0.9 | deleterious | None | None | None | None | N |
| V/F | 0.9052 | likely_pathogenic | 0.9183 | pathogenic | -1.422 | Destabilizing | 1.0 | D | 0.861 | deleterious | D | 0.571571201 | None | None | N |
| V/G | 0.889 | likely_pathogenic | 0.8905 | pathogenic | -3.266 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | D | 0.635055617 | None | None | N |
| V/H | 0.9978 | likely_pathogenic | 0.9978 | pathogenic | -2.945 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| V/I | 0.1062 | likely_benign | 0.1117 | benign | -1.099 | Destabilizing | 0.997 | D | 0.624 | neutral | D | 0.540124376 | None | None | N |
| V/K | 0.9949 | likely_pathogenic | 0.9944 | pathogenic | -2.012 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| V/L | 0.6675 | likely_pathogenic | 0.7236 | pathogenic | -1.099 | Destabilizing | 0.997 | D | 0.679 | prob.neutral | N | 0.505631733 | None | None | N |
| V/M | 0.7128 | likely_pathogenic | 0.7482 | pathogenic | -1.419 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| V/N | 0.9896 | likely_pathogenic | 0.9899 | pathogenic | -2.639 | Highly Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | None | N |
| V/P | 0.9926 | likely_pathogenic | 0.9923 | pathogenic | -1.626 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| V/Q | 0.9916 | likely_pathogenic | 0.9915 | pathogenic | -2.29 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| V/R | 0.9892 | likely_pathogenic | 0.9886 | pathogenic | -2.06 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| V/S | 0.9256 | likely_pathogenic | 0.9255 | pathogenic | -3.102 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| V/T | 0.7578 | likely_pathogenic | 0.7579 | pathogenic | -2.662 | Highly Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| V/W | 0.9982 | likely_pathogenic | 0.9984 | pathogenic | -1.864 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| V/Y | 0.9906 | likely_pathogenic | 0.9914 | pathogenic | -1.717 | Destabilizing | 1.0 | D | 0.85 | 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.