Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8603 | 26032;26033;26034 | chr2:178715607;178715606;178715605 | chr2:179580334;179580333;179580332 |
| N2AB | 8286 | 25081;25082;25083 | chr2:178715607;178715606;178715605 | chr2:179580334;179580333;179580332 |
| N2A | 7359 | 22300;22301;22302 | chr2:178715607;178715606;178715605 | chr2:179580334;179580333;179580332 |
| 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/L | rs781354478  |
0.144 | 0.934 | D | 0.581 | 0.372 | 0.684870435166 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| S/L | rs781354478 |
0.144 | 0.934 | D | 0.581 | 0.372 | 0.684870435166 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07814E-04 | 0 |
| S/L | rs781354478 |
0.144 | 0.934 | D | 0.581 | 0.372 | 0.684870435166 | gnomAD-4.0.0 | 6.81796E-06 | None | None | None | None | N | None | 1.33622E-05 | 0 | None | 0 | 2.22955E-05 | None | 0 | 0 | 4.23852E-06 | 4.3928E-05 | 0 |
| S/P | rs748398405 |
-0.758 | 0.826 | N | 0.611 | 0.378 | 0.352693368174 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/P | rs748398405 |
-0.758 | 0.826 | N | 0.611 | 0.378 | 0.352693368174 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs748398405 |
-0.758 | 0.826 | N | 0.611 | 0.378 | 0.352693368174 | gnomAD-4.0.0 | 6.57324E-06 | None | None | None | None | N | None | 2.4122E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/W | None | None | 0.998 | D | 0.706 | 0.487 | 0.797057192974 | gnomAD-4.0.0 | 6.84275E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99549E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0874 | likely_benign | 0.0844 | benign | -0.458 | Destabilizing | 0.01 | N | 0.462 | neutral | N | 0.491920527 | None | None | N |
| S/C | 0.2042 | likely_benign | 0.1974 | benign | -0.299 | Destabilizing | 0.986 | D | 0.602 | neutral | None | None | None | None | N |
| S/D | 0.5021 | ambiguous | 0.4628 | ambiguous | 0.431 | Stabilizing | 0.307 | N | 0.511 | neutral | None | None | None | None | N |
| S/E | 0.6497 | likely_pathogenic | 0.632 | pathogenic | 0.476 | Stabilizing | 0.553 | D | 0.547 | neutral | None | None | None | None | N |
| S/F | 0.213 | likely_benign | 0.2178 | benign | -0.697 | Destabilizing | 0.986 | D | 0.661 | neutral | None | None | None | None | N |
| S/G | 0.1093 | likely_benign | 0.1022 | benign | -0.723 | Destabilizing | 0.005 | N | 0.2 | neutral | None | None | None | None | N |
| S/H | 0.4285 | ambiguous | 0.415 | ambiguous | -1.027 | Destabilizing | 0.989 | D | 0.605 | neutral | None | None | None | None | N |
| S/I | 0.3441 | ambiguous | 0.3474 | ambiguous | 0.144 | Stabilizing | 0.921 | D | 0.654 | neutral | None | None | None | None | N |
| S/K | 0.7507 | likely_pathogenic | 0.7372 | pathogenic | -0.091 | Destabilizing | 0.768 | D | 0.543 | neutral | None | None | None | None | N |
| S/L | 0.0996 | likely_benign | 0.1008 | benign | 0.144 | Stabilizing | 0.934 | D | 0.581 | neutral | D | 0.534771698 | None | None | N |
| S/M | 0.1959 | likely_benign | 0.1957 | benign | 0.015 | Stabilizing | 0.996 | D | 0.599 | neutral | None | None | None | None | N |
| S/N | 0.2009 | likely_benign | 0.1865 | benign | -0.251 | Destabilizing | 0.001 | N | 0.277 | neutral | None | None | None | None | N |
| S/P | 0.6667 | likely_pathogenic | 0.6044 | pathogenic | -0.022 | Destabilizing | 0.826 | D | 0.611 | neutral | N | 0.511838889 | None | None | N |
| S/Q | 0.5902 | likely_pathogenic | 0.5825 | pathogenic | -0.215 | Destabilizing | 0.959 | D | 0.623 | neutral | None | None | None | None | N |
| S/R | 0.6901 | likely_pathogenic | 0.6784 | pathogenic | -0.166 | Destabilizing | 0.959 | D | 0.603 | neutral | None | None | None | None | N |
| S/T | 0.0986 | likely_benign | 0.0941 | benign | -0.248 | Destabilizing | 0.001 | N | 0.289 | neutral | D | 0.533982264 | None | None | N |
| S/V | 0.2843 | likely_benign | 0.2834 | benign | -0.022 | Destabilizing | 0.813 | D | 0.591 | neutral | None | None | None | None | N |
| S/W | 0.3874 | ambiguous | 0.3901 | ambiguous | -0.771 | Destabilizing | 0.998 | D | 0.706 | prob.neutral | D | 0.523866757 | None | None | N |
| S/Y | 0.1895 | likely_benign | 0.19 | benign | -0.397 | Destabilizing | 0.986 | D | 0.655 | neutral | 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.