Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14265 | 43018;43019;43020 | chr2:178633566;178633565;178633564 | chr2:179498293;179498292;179498291 |
| N2AB | 12624 | 38095;38096;38097 | chr2:178633566;178633565;178633564 | chr2:179498293;179498292;179498291 |
| N2A | 11697 | 35314;35315;35316 | chr2:178633566;178633565;178633564 | chr2:179498293;179498292;179498291 |
| N2B | 5200 | 15823;15824;15825 | chr2:178633566;178633565;178633564 | chr2:179498293;179498292;179498291 |
| Novex-1 | 5325 | 16198;16199;16200 | chr2:178633566;178633565;178633564 | chr2:179498293;179498292;179498291 |
| Novex-2 | 5392 | 16399;16400;16401 | chr2:178633566;178633565;178633564 | chr2:179498293;179498292;179498291 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs1009314740  |
-0.612 | 0.955 | N | 0.515 | 0.385 | 0.286081765059 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/G | rs1009314740 |
-0.612 | 0.955 | N | 0.515 | 0.385 | 0.286081765059 | 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 |
| D/G | rs1009314740 |
-0.612 | 0.955 | N | 0.515 | 0.385 | 0.286081765059 | gnomAD-4.0.0 | 3.0992E-06 | None | None | None | None | N | None | 5.34045E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60179E-05 |
| D/N | rs758416170 |
-0.3 | 0.117 | N | 0.288 | 0.15 | 0.228597637076 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| D/Y | rs758416170 |
-0.004 | 1.0 | D | 0.662 | 0.429 | 0.537356456974 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| D/Y | rs758416170 |
-0.004 | 1.0 | D | 0.662 | 0.429 | 0.537356456974 | gnomAD-4.0.0 | 1.5922E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78133E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2046 | likely_benign | 0.1908 | benign | -0.53 | Destabilizing | 0.993 | D | 0.581 | neutral | D | 0.636142987 | None | None | N |
| D/C | 0.6575 | likely_pathogenic | 0.6666 | pathogenic | -0.179 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| D/E | 0.2319 | likely_benign | 0.2402 | benign | -0.438 | Destabilizing | 0.977 | D | 0.371 | neutral | N | 0.484520159 | None | None | N |
| D/F | 0.7264 | likely_pathogenic | 0.6629 | pathogenic | -0.22 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| D/G | 0.1369 | likely_benign | 0.1353 | benign | -0.793 | Destabilizing | 0.955 | D | 0.515 | neutral | N | 0.468520725 | None | None | N |
| D/H | 0.4378 | ambiguous | 0.4005 | ambiguous | -0.209 | Destabilizing | 0.999 | D | 0.594 | neutral | D | 0.712573615 | None | None | N |
| D/I | 0.6541 | likely_pathogenic | 0.5534 | ambiguous | 0.14 | Stabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | N |
| D/K | 0.5213 | ambiguous | 0.4829 | ambiguous | -0.026 | Destabilizing | 0.995 | D | 0.567 | neutral | None | None | None | None | N |
| D/L | 0.5575 | ambiguous | 0.5271 | ambiguous | 0.14 | Stabilizing | 0.998 | D | 0.667 | neutral | None | None | None | None | N |
| D/M | 0.7494 | likely_pathogenic | 0.723 | pathogenic | 0.364 | Stabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| D/N | 0.0879 | likely_benign | 0.0827 | benign | -0.425 | Destabilizing | 0.117 | N | 0.288 | neutral | N | 0.437378247 | None | None | N |
| D/P | 0.9699 | likely_pathogenic | 0.9624 | pathogenic | -0.06 | Destabilizing | 0.999 | D | 0.592 | neutral | None | None | None | None | N |
| D/Q | 0.4602 | ambiguous | 0.4695 | ambiguous | -0.351 | Destabilizing | 0.998 | D | 0.538 | neutral | None | None | None | None | N |
| D/R | 0.567 | likely_pathogenic | 0.5214 | ambiguous | 0.216 | Stabilizing | 0.995 | D | 0.602 | neutral | None | None | None | None | N |
| D/S | 0.1585 | likely_benign | 0.1461 | benign | -0.578 | Destabilizing | 0.966 | D | 0.461 | neutral | None | None | None | None | N |
| D/T | 0.4362 | ambiguous | 0.3819 | ambiguous | -0.366 | Destabilizing | 0.995 | D | 0.564 | neutral | None | None | None | None | N |
| D/V | 0.4249 | ambiguous | 0.3442 | ambiguous | -0.06 | Destabilizing | 0.997 | D | 0.671 | neutral | D | 0.676198009 | None | None | N |
| D/W | 0.9208 | likely_pathogenic | 0.9046 | pathogenic | None | Stabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | N |
| D/Y | 0.2979 | likely_benign | 0.2364 | benign | 0.03 | Stabilizing | 1.0 | D | 0.662 | neutral | D | 0.712684359 | 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.