Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29279 | 88060;88061;88062 | chr2:178557427;178557426;178557425 | chr2:179422154;179422153;179422152 |
| N2AB | 27638 | 83137;83138;83139 | chr2:178557427;178557426;178557425 | chr2:179422154;179422153;179422152 |
| N2A | 26711 | 80356;80357;80358 | chr2:178557427;178557426;178557425 | chr2:179422154;179422153;179422152 |
| N2B | 20214 | 60865;60866;60867 | chr2:178557427;178557426;178557425 | chr2:179422154;179422153;179422152 |
| Novex-1 | 20339 | 61240;61241;61242 | chr2:178557427;178557426;178557425 | chr2:179422154;179422153;179422152 |
| Novex-2 | 20406 | 61441;61442;61443 | chr2:178557427;178557426;178557425 | chr2:179422154;179422153;179422152 |
| 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/K | None | None | 0.219 | N | 0.202 | 0.159 | 0.224531998449 | gnomAD-4.0.0 | 6.84164E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15934E-05 | 0 |
| R/S | rs184963961  |
-0.564 | 0.98 | N | 0.629 | 0.33 | 0.236890367714 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| R/T | rs773541746 |
-0.252 | 0.99 | N | 0.583 | 0.332 | 0.344483371355 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/T | rs773541746 |
-0.252 | 0.99 | N | 0.583 | 0.332 | 0.344483371355 | gnomAD-4.0.0 | 6.15748E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.09479E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7942 | likely_pathogenic | 0.8684 | pathogenic | -0.43 | Destabilizing | 0.985 | D | 0.619 | neutral | None | None | None | None | N |
| R/C | 0.3858 | ambiguous | 0.4984 | ambiguous | -0.31 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| R/D | 0.958 | likely_pathogenic | 0.9761 | pathogenic | -0.006 | Destabilizing | 0.998 | D | 0.638 | neutral | None | None | None | None | N |
| R/E | 0.7677 | likely_pathogenic | 0.8352 | pathogenic | 0.101 | Stabilizing | 0.985 | D | 0.598 | neutral | None | None | None | None | N |
| R/F | 0.9205 | likely_pathogenic | 0.9512 | pathogenic | -0.406 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/G | 0.6509 | likely_pathogenic | 0.7669 | pathogenic | -0.719 | Destabilizing | 0.99 | D | 0.617 | neutral | N | 0.487734607 | None | None | N |
| R/H | 0.2743 | likely_benign | 0.3452 | ambiguous | -1.236 | Destabilizing | 0.999 | D | 0.569 | neutral | None | None | None | None | N |
| R/I | 0.6553 | likely_pathogenic | 0.7321 | pathogenic | 0.329 | Stabilizing | 0.999 | D | 0.705 | prob.neutral | N | 0.500586474 | None | None | N |
| R/K | 0.1835 | likely_benign | 0.194 | benign | -0.433 | Destabilizing | 0.219 | N | 0.202 | neutral | N | 0.396496527 | None | None | N |
| R/L | 0.6457 | likely_pathogenic | 0.7407 | pathogenic | 0.329 | Stabilizing | 0.993 | D | 0.617 | neutral | None | None | None | None | N |
| R/M | 0.6762 | likely_pathogenic | 0.7639 | pathogenic | 0.001 | Stabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | N |
| R/N | 0.9107 | likely_pathogenic | 0.9414 | pathogenic | 0.064 | Stabilizing | 0.998 | D | 0.544 | neutral | None | None | None | None | N |
| R/P | 0.8945 | likely_pathogenic | 0.9519 | pathogenic | 0.098 | Stabilizing | 0.999 | D | 0.696 | prob.neutral | None | None | None | None | N |
| R/Q | 0.1904 | likely_benign | 0.228 | benign | -0.089 | Destabilizing | 0.996 | D | 0.575 | neutral | None | None | None | None | N |
| R/S | 0.869 | likely_pathogenic | 0.9163 | pathogenic | -0.548 | Destabilizing | 0.98 | D | 0.629 | neutral | N | 0.480056487 | None | None | N |
| R/T | 0.6964 | likely_pathogenic | 0.792 | pathogenic | -0.268 | Destabilizing | 0.99 | D | 0.583 | neutral | N | 0.480787205 | None | None | N |
| R/V | 0.7413 | likely_pathogenic | 0.8054 | pathogenic | 0.098 | Stabilizing | 0.998 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/W | 0.4766 | ambiguous | 0.5998 | pathogenic | -0.205 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| R/Y | 0.8021 | likely_pathogenic | 0.8635 | pathogenic | 0.14 | Stabilizing | 0.999 | D | 0.697 | prob.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.