Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23479 | 70660;70661;70662 | chr2:178575697;178575696;178575695 | chr2:179440424;179440423;179440422 |
| N2AB | 21838 | 65737;65738;65739 | chr2:178575697;178575696;178575695 | chr2:179440424;179440423;179440422 |
| N2A | 20911 | 62956;62957;62958 | chr2:178575697;178575696;178575695 | chr2:179440424;179440423;179440422 |
| N2B | 14414 | 43465;43466;43467 | chr2:178575697;178575696;178575695 | chr2:179440424;179440423;179440422 |
| Novex-1 | 14539 | 43840;43841;43842 | chr2:178575697;178575696;178575695 | chr2:179440424;179440423;179440422 |
| Novex-2 | 14606 | 44041;44042;44043 | chr2:178575697;178575696;178575695 | chr2:179440424;179440423;179440422 |
| 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/Q | rs140127488  |
0.072 | 0.998 | N | 0.36 | 0.244 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.78E-05 | 0 |
| R/Q | rs140127488 |
0.072 | 0.998 | N | 0.36 | 0.244 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94099E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs140127488 |
0.072 | 0.998 | N | 0.36 | 0.244 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/Q | rs140127488 |
0.072 | 0.998 | N | 0.36 | 0.244 | None | gnomAD-4.0.0 | 1.54944E-05 | None | None | None | None | N | None | 1.33316E-05 | 0 | None | 0 | 2.23454E-05 | None | 0 | 0 | 1.69545E-05 | 3.29417E-05 | 0 |
| R/W | rs760509116 |
-0.376 | 1.0 | N | 0.647 | 0.328 | 0.370424759081 | gnomAD-2.1.1 | 6.08E-05 | None | None | None | None | N | None | 4.13E-05 | 3.67876E-04 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| R/W | rs760509116 |
-0.376 | 1.0 | N | 0.647 | 0.328 | 0.370424759081 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 1.96773E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/W | rs760509116 |
-0.376 | 1.0 | N | 0.647 | 0.328 | 0.370424759081 | gnomAD-4.0.0 | 3.09884E-05 | None | None | None | None | N | None | 3.99957E-05 | 3.16772E-04 | None | 0 | 0 | None | 0 | 0 | 1.86498E-05 | 2.19602E-05 | 6.40307E-05 |
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 | 0.9378 | likely_pathogenic | 0.9276 | pathogenic | -0.619 | Destabilizing | 0.982 | D | 0.368 | neutral | None | None | None | None | N |
| R/C | 0.6057 | likely_pathogenic | 0.5919 | pathogenic | -0.571 | Destabilizing | 1.0 | D | 0.618 | neutral | None | None | None | None | N |
| R/D | 0.9892 | likely_pathogenic | 0.9867 | pathogenic | -0.023 | Destabilizing | 0.997 | D | 0.427 | neutral | None | None | None | None | N |
| R/E | 0.933 | likely_pathogenic | 0.9273 | pathogenic | 0.054 | Stabilizing | 0.944 | D | 0.299 | neutral | None | None | None | None | N |
| R/F | 0.952 | likely_pathogenic | 0.9505 | pathogenic | -0.727 | Destabilizing | 0.998 | D | 0.556 | neutral | None | None | None | None | N |
| R/G | 0.8161 | likely_pathogenic | 0.784 | pathogenic | -0.86 | Destabilizing | 0.995 | D | 0.361 | neutral | N | 0.507568375 | None | None | N |
| R/H | 0.3978 | ambiguous | 0.3852 | ambiguous | -1.169 | Destabilizing | 0.998 | D | 0.321 | neutral | None | None | None | None | N |
| R/I | 0.9212 | likely_pathogenic | 0.9118 | pathogenic | 0.003 | Stabilizing | 0.998 | D | 0.559 | neutral | None | None | None | None | N |
| R/K | 0.2454 | likely_benign | 0.2194 | benign | -0.601 | Destabilizing | 0.036 | N | 0.203 | neutral | None | None | None | None | N |
| R/L | 0.8029 | likely_pathogenic | 0.777 | pathogenic | 0.003 | Stabilizing | 0.989 | D | 0.361 | neutral | N | 0.48616813 | None | None | N |
| R/M | 0.8195 | likely_pathogenic | 0.8117 | pathogenic | -0.208 | Destabilizing | 0.999 | D | 0.388 | neutral | None | None | None | None | N |
| R/N | 0.9739 | likely_pathogenic | 0.9696 | pathogenic | -0.055 | Destabilizing | 0.997 | D | 0.323 | neutral | None | None | None | None | N |
| R/P | 0.9928 | likely_pathogenic | 0.9915 | pathogenic | -0.184 | Destabilizing | 1.0 | D | 0.482 | neutral | N | 0.47992716 | None | None | N |
| R/Q | 0.3477 | ambiguous | 0.3334 | benign | -0.311 | Destabilizing | 0.998 | D | 0.36 | neutral | N | 0.478913202 | None | None | N |
| R/S | 0.9598 | likely_pathogenic | 0.9521 | pathogenic | -0.759 | Destabilizing | 0.982 | D | 0.381 | neutral | None | None | None | None | N |
| R/T | 0.9298 | likely_pathogenic | 0.9118 | pathogenic | -0.528 | Destabilizing | 0.991 | D | 0.367 | neutral | None | None | None | None | N |
| R/V | 0.9272 | likely_pathogenic | 0.918 | pathogenic | -0.184 | Destabilizing | 0.992 | D | 0.539 | neutral | None | None | None | None | N |
| R/W | 0.6242 | likely_pathogenic | 0.6303 | pathogenic | -0.501 | Destabilizing | 1.0 | D | 0.647 | neutral | N | 0.480687628 | None | None | N |
| R/Y | 0.8865 | likely_pathogenic | 0.8874 | pathogenic | -0.162 | Destabilizing | 0.998 | D | 0.483 | 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.