Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30579 | 91960;91961;91962 | chr2:178550103;178550102;178550101 | chr2:179414830;179414829;179414828 |
| N2AB | 28938 | 87037;87038;87039 | chr2:178550103;178550102;178550101 | chr2:179414830;179414829;179414828 |
| N2A | 28011 | 84256;84257;84258 | chr2:178550103;178550102;178550101 | chr2:179414830;179414829;179414828 |
| N2B | 21514 | 64765;64766;64767 | chr2:178550103;178550102;178550101 | chr2:179414830;179414829;179414828 |
| Novex-1 | 21639 | 65140;65141;65142 | chr2:178550103;178550102;178550101 | chr2:179414830;179414829;179414828 |
| Novex-2 | 21706 | 65341;65342;65343 | chr2:178550103;178550102;178550101 | chr2:179414830;179414829;179414828 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | None | None | 0.982 | N | 0.439 | 0.193 | 0.344017737713 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| L/P | rs765022890  |
-0.188 | 0.997 | N | 0.552 | 0.425 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| L/P | rs765022890 |
-0.188 | 0.997 | N | 0.552 | 0.425 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | rs765022890 |
-0.188 | 0.997 | N | 0.552 | 0.425 | None | gnomAD-4.0.0 | 3.7182E-06 | None | None | None | None | I | None | 4.00641E-05 | 0 | None | 0 | 6.68479E-05 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | None | None | 0.76 | N | 0.446 | 0.084 | 0.262662153117 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.269 | likely_benign | 0.2775 | benign | -0.597 | Destabilizing | 0.953 | D | 0.461 | neutral | None | None | None | None | I |
| L/C | 0.6771 | likely_pathogenic | 0.6769 | pathogenic | -1.016 | Destabilizing | 0.999 | D | 0.477 | neutral | None | None | None | None | I |
| L/D | 0.7942 | likely_pathogenic | 0.7888 | pathogenic | -0.207 | Destabilizing | 0.998 | D | 0.554 | neutral | None | None | None | None | I |
| L/E | 0.5472 | ambiguous | 0.545 | ambiguous | -0.287 | Destabilizing | 0.998 | D | 0.547 | neutral | None | None | None | None | I |
| L/F | 0.2254 | likely_benign | 0.2268 | benign | -0.751 | Destabilizing | 0.982 | D | 0.439 | neutral | N | 0.444201969 | None | None | I |
| L/G | 0.6475 | likely_pathogenic | 0.6501 | pathogenic | -0.67 | Destabilizing | 0.998 | D | 0.545 | neutral | None | None | None | None | I |
| L/H | 0.4108 | ambiguous | 0.409 | ambiguous | -0.064 | Destabilizing | 0.999 | D | 0.575 | neutral | N | 0.462614371 | None | None | I |
| L/I | 0.1036 | likely_benign | 0.1112 | benign | -0.51 | Destabilizing | 0.02 | N | 0.329 | neutral | N | 0.42255726 | None | None | I |
| L/K | 0.4727 | ambiguous | 0.4587 | ambiguous | -0.471 | Destabilizing | 0.993 | D | 0.49 | neutral | None | None | None | None | I |
| L/M | 0.1544 | likely_benign | 0.1577 | benign | -0.801 | Destabilizing | 0.986 | D | 0.456 | neutral | None | None | None | None | I |
| L/N | 0.5304 | ambiguous | 0.5352 | ambiguous | -0.401 | Destabilizing | 0.998 | D | 0.552 | neutral | None | None | None | None | I |
| L/P | 0.1897 | likely_benign | 0.1978 | benign | -0.515 | Destabilizing | 0.997 | D | 0.552 | neutral | N | 0.393869149 | None | None | I |
| L/Q | 0.2954 | likely_benign | 0.2901 | benign | -0.526 | Destabilizing | 0.998 | D | 0.498 | neutral | None | None | None | None | I |
| L/R | 0.3595 | ambiguous | 0.3499 | ambiguous | -0.072 | Destabilizing | 0.997 | D | 0.499 | neutral | N | 0.437582641 | None | None | I |
| L/S | 0.4005 | ambiguous | 0.3994 | ambiguous | -0.794 | Destabilizing | 0.993 | D | 0.478 | neutral | None | None | None | None | I |
| L/T | 0.2647 | likely_benign | 0.2777 | benign | -0.779 | Destabilizing | 0.986 | D | 0.397 | neutral | None | None | None | None | I |
| L/V | 0.1274 | likely_benign | 0.1353 | benign | -0.515 | Destabilizing | 0.76 | D | 0.446 | neutral | N | 0.462961088 | None | None | I |
| L/W | 0.3721 | ambiguous | 0.3845 | ambiguous | -0.749 | Destabilizing | 0.999 | D | 0.591 | neutral | None | None | None | None | I |
| L/Y | 0.4944 | ambiguous | 0.4936 | ambiguous | -0.56 | Destabilizing | 0.998 | D | 0.439 | neutral | None | None | None | None | I |
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.