Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15292 | 46099;46100;46101 | chr2:178620736;178620735;178620734 | chr2:179485463;179485462;179485461 |
| N2AB | 13651 | 41176;41177;41178 | chr2:178620736;178620735;178620734 | chr2:179485463;179485462;179485461 |
| N2A | 12724 | 38395;38396;38397 | chr2:178620736;178620735;178620734 | chr2:179485463;179485462;179485461 |
| N2B | 6227 | 18904;18905;18906 | chr2:178620736;178620735;178620734 | chr2:179485463;179485462;179485461 |
| Novex-1 | 6352 | 19279;19280;19281 | chr2:178620736;178620735;178620734 | chr2:179485463;179485462;179485461 |
| Novex-2 | 6419 | 19480;19481;19482 | chr2:178620736;178620735;178620734 | chr2:179485463;179485462;179485461 |
| 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/T | None | None | 0.022 | N | 0.162 | 0.046 | 0.251116650651 | gnomAD-4.0.0 | 6.8465E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99944E-07 | 0 | 0 |
| A/V | rs1419332401  |
None | 0.801 | N | 0.488 | 0.208 | 0.511907979761 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs1419332401 |
None | 0.801 | N | 0.488 | 0.208 | 0.511907979761 | gnomAD-4.0.0 | 1.31621E-05 | None | None | None | None | N | None | 4.83162E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4337 | ambiguous | 0.4378 | ambiguous | -0.822 | Destabilizing | 0.998 | D | 0.587 | neutral | None | None | None | None | N |
| A/D | 0.2528 | likely_benign | 0.2542 | benign | -1.178 | Destabilizing | 0.728 | D | 0.629 | neutral | None | None | None | None | N |
| A/E | 0.2094 | likely_benign | 0.2065 | benign | -1.312 | Destabilizing | 0.801 | D | 0.568 | neutral | N | 0.453240901 | None | None | N |
| A/F | 0.2624 | likely_benign | 0.2669 | benign | -1.298 | Destabilizing | 0.991 | D | 0.678 | prob.neutral | None | None | None | None | N |
| A/G | 0.1582 | likely_benign | 0.1628 | benign | -0.837 | Destabilizing | 0.454 | N | 0.441 | neutral | N | 0.511578919 | None | None | N |
| A/H | 0.3764 | ambiguous | 0.3836 | ambiguous | -0.949 | Destabilizing | 0.974 | D | 0.653 | neutral | None | None | None | None | N |
| A/I | 0.2035 | likely_benign | 0.2244 | benign | -0.589 | Destabilizing | 0.842 | D | 0.644 | neutral | None | None | None | None | N |
| A/K | 0.3266 | likely_benign | 0.3307 | benign | -0.973 | Destabilizing | 0.842 | D | 0.569 | neutral | None | None | None | None | N |
| A/L | 0.1806 | likely_benign | 0.1976 | benign | -0.589 | Destabilizing | 0.842 | D | 0.575 | neutral | None | None | None | None | N |
| A/M | 0.1953 | likely_benign | 0.2078 | benign | -0.344 | Destabilizing | 0.991 | D | 0.615 | neutral | None | None | None | None | N |
| A/N | 0.2125 | likely_benign | 0.2234 | benign | -0.624 | Destabilizing | 0.067 | N | 0.398 | neutral | None | None | None | None | N |
| A/P | 0.5326 | ambiguous | 0.5837 | pathogenic | -0.597 | Destabilizing | 0.891 | D | 0.647 | neutral | N | 0.5129643 | None | None | N |
| A/Q | 0.2639 | likely_benign | 0.2681 | benign | -0.962 | Destabilizing | 0.974 | D | 0.648 | neutral | None | None | None | None | N |
| A/R | 0.2819 | likely_benign | 0.2864 | benign | -0.46 | Destabilizing | 0.842 | D | 0.634 | neutral | None | None | None | None | N |
| A/S | 0.0823 | likely_benign | 0.0813 | benign | -0.825 | Destabilizing | 0.007 | N | 0.146 | neutral | N | 0.368139889 | None | None | N |
| A/T | 0.0716 | likely_benign | 0.0737 | benign | -0.889 | Destabilizing | 0.022 | N | 0.162 | neutral | N | 0.455371771 | None | None | N |
| A/V | 0.1133 | likely_benign | 0.1187 | benign | -0.597 | Destabilizing | 0.801 | D | 0.488 | neutral | N | 0.509008629 | None | None | N |
| A/W | 0.6604 | likely_pathogenic | 0.6759 | pathogenic | -1.464 | Destabilizing | 0.998 | D | 0.671 | neutral | None | None | None | None | N |
| A/Y | 0.3924 | ambiguous | 0.4079 | ambiguous | -1.111 | Destabilizing | 0.991 | D | 0.673 | 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.