Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9574 | 28945;28946;28947 | chr2:178709599;178709598;178709597 | chr2:179574326;179574325;179574324 |
| N2AB | 9257 | 27994;27995;27996 | chr2:178709599;178709598;178709597 | chr2:179574326;179574325;179574324 |
| N2A | 8330 | 25213;25214;25215 | chr2:178709599;178709598;178709597 | chr2:179574326;179574325;179574324 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs376276989  |
-0.014 | 0.999 | None | 0.487 | 0.504 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/C | rs376276989 |
-0.014 | 0.999 | None | 0.487 | 0.504 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/C | rs376276989 |
-0.014 | 0.999 | None | 0.487 | 0.504 | None | gnomAD-4.0.0 | 2.02972E-06 | None | None | None | None | I | None | 1.74648E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.20489E-06 | 0 | 0 |
| S/F | rs376276989 |
None | 0.996 | None | 0.537 | 0.535 | 0.779969046472 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1386 | likely_benign | 0.1124 | benign | -0.398 | Destabilizing | 0.826 | D | 0.241 | neutral | None | None | None | None | I |
| S/C | 0.2381 | likely_benign | 0.2119 | benign | -0.311 | Destabilizing | 0.999 | D | 0.487 | neutral | None | None | None | None | I |
| S/D | 0.6948 | likely_pathogenic | 0.632 | pathogenic | 0.151 | Stabilizing | 0.884 | D | 0.261 | neutral | None | None | None | None | I |
| S/E | 0.7153 | likely_pathogenic | 0.6767 | pathogenic | 0.057 | Stabilizing | 0.17 | N | 0.109 | neutral | None | None | None | None | I |
| S/F | 0.3057 | likely_benign | 0.2462 | benign | -0.979 | Destabilizing | 0.996 | D | 0.537 | neutral | None | None | None | None | I |
| S/G | 0.2155 | likely_benign | 0.1766 | benign | -0.509 | Destabilizing | 0.927 | D | 0.284 | neutral | None | None | None | None | I |
| S/H | 0.5696 | likely_pathogenic | 0.5492 | ambiguous | -0.968 | Destabilizing | 0.997 | D | 0.491 | neutral | None | None | None | None | I |
| S/I | 0.3425 | ambiguous | 0.2653 | benign | -0.237 | Destabilizing | 0.982 | D | 0.517 | neutral | None | None | None | None | I |
| S/K | 0.9052 | likely_pathogenic | 0.8865 | pathogenic | -0.488 | Destabilizing | 0.17 | N | 0.107 | neutral | None | None | None | None | I |
| S/L | 0.1881 | likely_benign | 0.1549 | benign | -0.237 | Destabilizing | 0.939 | D | 0.513 | neutral | None | None | None | None | I |
| S/M | 0.3307 | likely_benign | 0.253 | benign | -0.016 | Destabilizing | 0.997 | D | 0.49 | neutral | None | None | None | None | I |
| S/N | 0.2587 | likely_benign | 0.2009 | benign | -0.193 | Destabilizing | 0.969 | D | 0.305 | neutral | None | None | None | None | I |
| S/P | 0.9068 | likely_pathogenic | 0.8971 | pathogenic | -0.262 | Destabilizing | 0.986 | D | 0.465 | neutral | None | None | None | None | I |
| S/Q | 0.716 | likely_pathogenic | 0.6964 | pathogenic | -0.449 | Destabilizing | 0.939 | D | 0.385 | neutral | None | None | None | None | I |
| S/R | 0.8534 | likely_pathogenic | 0.843 | pathogenic | -0.256 | Destabilizing | 0.046 | N | 0.243 | neutral | None | None | None | None | I |
| S/T | 0.1128 | likely_benign | 0.092 | benign | -0.316 | Destabilizing | 0.134 | N | 0.1 | neutral | None | None | None | None | I |
| S/V | 0.3238 | likely_benign | 0.2432 | benign | -0.262 | Destabilizing | 0.939 | D | 0.493 | neutral | None | None | None | None | I |
| S/W | 0.5674 | likely_pathogenic | 0.5525 | ambiguous | -0.977 | Destabilizing | 0.999 | D | 0.563 | neutral | None | None | None | None | I |
| S/Y | 0.3126 | likely_benign | 0.2848 | benign | -0.701 | Destabilizing | 0.996 | D | 0.539 | 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.