Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35670 | 107233;107234;107235 | chr2:178528743;178528742;178528741 | chr2:179393470;179393469;179393468 |
| N2AB | 34029 | 102310;102311;102312 | chr2:178528743;178528742;178528741 | chr2:179393470;179393469;179393468 |
| N2A | 33102 | 99529;99530;99531 | chr2:178528743;178528742;178528741 | chr2:179393470;179393469;179393468 |
| N2B | 26605 | 80038;80039;80040 | chr2:178528743;178528742;178528741 | chr2:179393470;179393469;179393468 |
| Novex-1 | 26730 | 80413;80414;80415 | chr2:178528743;178528742;178528741 | chr2:179393470;179393469;179393468 |
| Novex-2 | 26797 | 80614;80615;80616 | chr2:178528743;178528742;178528741 | chr2:179393470;179393469;179393468 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 0.024 | N | 0.368 | 0.066 | 0.273503213844 | gnomAD-4.0.0 | 1.59281E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4339E-05 | 0 |
| R/T | rs534961012  |
0.228 | 0.055 | N | 0.397 | 0.064 | None | gnomAD-2.1.1 | 3.58E-05 | None | None | None | None | I | None | 3.31318E-04 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 1.40885E-04 |
| R/T | rs534961012 |
0.228 | 0.055 | N | 0.397 | 0.064 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | I | None | 1.44823E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs534961012 |
0.228 | 0.055 | N | 0.397 | 0.064 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/T | rs534961012 |
0.228 | 0.055 | N | 0.397 | 0.064 | None | gnomAD-4.0.0 | 3.34728E-05 | None | None | None | None | I | None | 5.06478E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.29547E-05 | 2.0814E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2161 | likely_benign | 0.2403 | benign | 0.185 | Stabilizing | 0.016 | N | 0.359 | neutral | None | None | None | None | I |
| R/C | 0.3025 | likely_benign | 0.3936 | ambiguous | 0.132 | Stabilizing | 0.864 | D | 0.275 | neutral | None | None | None | None | I |
| R/D | 0.4484 | ambiguous | 0.4764 | ambiguous | -0.112 | Destabilizing | 0.072 | N | 0.423 | neutral | None | None | None | None | I |
| R/E | 0.2155 | likely_benign | 0.2356 | benign | -0.051 | Destabilizing | 0.016 | N | 0.343 | neutral | None | None | None | None | I |
| R/F | 0.5107 | ambiguous | 0.5491 | ambiguous | -0.054 | Destabilizing | 0.356 | N | 0.339 | neutral | None | None | None | None | I |
| R/G | 0.1347 | likely_benign | 0.1594 | benign | -0.001 | Destabilizing | 0.024 | N | 0.368 | neutral | N | 0.437929357 | None | None | I |
| R/H | 0.1352 | likely_benign | 0.1405 | benign | -0.668 | Destabilizing | None | N | 0.185 | neutral | None | None | None | None | I |
| R/I | 0.1942 | likely_benign | 0.2245 | benign | 0.637 | Stabilizing | 0.295 | N | 0.359 | neutral | N | 0.439316224 | None | None | I |
| R/K | 0.0654 | likely_benign | 0.0682 | benign | 0.164 | Stabilizing | None | N | 0.168 | neutral | N | 0.408126525 | None | None | I |
| R/L | 0.2151 | likely_benign | 0.2338 | benign | 0.637 | Stabilizing | 0.072 | N | 0.377 | neutral | None | None | None | None | I |
| R/M | 0.1927 | likely_benign | 0.2166 | benign | 0.164 | Stabilizing | 0.628 | D | 0.332 | neutral | None | None | None | None | I |
| R/N | 0.3709 | ambiguous | 0.3932 | ambiguous | 0.39 | Stabilizing | 0.031 | N | 0.339 | neutral | None | None | None | None | I |
| R/P | 0.5866 | likely_pathogenic | 0.607 | pathogenic | 0.507 | Stabilizing | 0.136 | N | 0.41 | neutral | None | None | None | None | I |
| R/Q | 0.098 | likely_benign | 0.1041 | benign | 0.323 | Stabilizing | 0.038 | N | 0.375 | neutral | None | None | None | None | I |
| R/S | 0.2617 | likely_benign | 0.2931 | benign | 0.165 | Stabilizing | 0.012 | N | 0.373 | neutral | N | 0.435328982 | None | None | I |
| R/T | 0.1263 | likely_benign | 0.1399 | benign | 0.352 | Stabilizing | 0.055 | N | 0.397 | neutral | N | 0.438102716 | None | None | I |
| R/V | 0.2714 | likely_benign | 0.3046 | benign | 0.507 | Stabilizing | 0.072 | N | 0.435 | neutral | None | None | None | None | I |
| R/W | 0.2051 | likely_benign | 0.2265 | benign | -0.196 | Destabilizing | 0.864 | D | 0.271 | neutral | None | None | None | None | I |
| R/Y | 0.4198 | ambiguous | 0.4521 | ambiguous | 0.228 | Stabilizing | 0.072 | N | 0.418 | 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.