Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27052 | 81379;81380;81381 | chr2:178564978;178564977;178564976 | chr2:179429705;179429704;179429703 |
| N2AB | 25411 | 76456;76457;76458 | chr2:178564978;178564977;178564976 | chr2:179429705;179429704;179429703 |
| N2A | 24484 | 73675;73676;73677 | chr2:178564978;178564977;178564976 | chr2:179429705;179429704;179429703 |
| N2B | 17987 | 54184;54185;54186 | chr2:178564978;178564977;178564976 | chr2:179429705;179429704;179429703 |
| Novex-1 | 18112 | 54559;54560;54561 | chr2:178564978;178564977;178564976 | chr2:179429705;179429704;179429703 |
| Novex-2 | 18179 | 54760;54761;54762 | chr2:178564978;178564977;178564976 | chr2:179429705;179429704;179429703 |
| 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/S | None | None | 0.892 | N | 0.578 | 0.209 | 0.141422826196 | gnomAD-4.0.0 | 6.85158E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00132E-07 | 0 | 0 |
| R/T | rs762209719  |
0.202 | 0.967 | N | 0.525 | 0.437 | 0.368554958709 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 9.35E-05 | 8.94E-06 | 0 |
| R/T | rs762209719 |
0.202 | 0.967 | N | 0.525 | 0.437 | 0.368554958709 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 2.82592E-04 | 0 | 0 | 0 | 0 |
| R/T | rs762209719 |
0.202 | 0.967 | N | 0.525 | 0.437 | 0.368554958709 | gnomAD-4.0.0 | 1.67018E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.88495E-04 | 0 | 2.39835E-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 | 0.9867 | likely_pathogenic | 0.9859 | pathogenic | 0.091 | Stabilizing | 0.845 | D | 0.608 | neutral | None | None | None | None | I |
| R/C | 0.87 | likely_pathogenic | 0.8823 | pathogenic | -0.116 | Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | I |
| R/D | 0.9963 | likely_pathogenic | 0.996 | pathogenic | -0.228 | Destabilizing | 0.975 | D | 0.567 | neutral | None | None | None | None | I |
| R/E | 0.9852 | likely_pathogenic | 0.9844 | pathogenic | -0.16 | Destabilizing | 0.845 | D | 0.57 | neutral | None | None | None | None | I |
| R/F | 0.9892 | likely_pathogenic | 0.9898 | pathogenic | -0.182 | Destabilizing | 0.996 | D | 0.611 | neutral | None | None | None | None | I |
| R/G | 0.979 | likely_pathogenic | 0.9764 | pathogenic | -0.088 | Destabilizing | 0.892 | D | 0.509 | neutral | N | 0.459231422 | None | None | I |
| R/H | 0.7324 | likely_pathogenic | 0.7323 | pathogenic | -0.805 | Destabilizing | 0.987 | D | 0.545 | neutral | None | None | None | None | I |
| R/I | 0.9421 | likely_pathogenic | 0.9493 | pathogenic | 0.523 | Stabilizing | 0.987 | D | 0.613 | neutral | None | None | None | None | I |
| R/K | 0.6319 | likely_pathogenic | 0.5966 | pathogenic | -0.011 | Destabilizing | 0.025 | N | 0.344 | neutral | N | 0.467108619 | None | None | I |
| R/L | 0.9316 | likely_pathogenic | 0.9332 | pathogenic | 0.523 | Stabilizing | 0.916 | D | 0.509 | neutral | None | None | None | None | I |
| R/M | 0.971 | likely_pathogenic | 0.9732 | pathogenic | -0.021 | Destabilizing | 0.999 | D | 0.543 | neutral | D | 0.52325269 | None | None | I |
| R/N | 0.9904 | likely_pathogenic | 0.9897 | pathogenic | 0.082 | Stabilizing | 0.975 | D | 0.527 | neutral | None | None | None | None | I |
| R/P | 0.9883 | likely_pathogenic | 0.9845 | pathogenic | 0.399 | Stabilizing | 0.987 | D | 0.58 | neutral | None | None | None | None | I |
| R/Q | 0.7586 | likely_pathogenic | 0.7468 | pathogenic | 0.07 | Stabilizing | 0.975 | D | 0.532 | neutral | None | None | None | None | I |
| R/S | 0.9907 | likely_pathogenic | 0.9894 | pathogenic | -0.107 | Destabilizing | 0.892 | D | 0.578 | neutral | N | 0.493583144 | None | None | I |
| R/T | 0.9825 | likely_pathogenic | 0.9813 | pathogenic | 0.09 | Stabilizing | 0.967 | D | 0.525 | neutral | N | 0.46818878 | None | None | I |
| R/V | 0.9706 | likely_pathogenic | 0.9709 | pathogenic | 0.399 | Stabilizing | 0.975 | D | 0.602 | neutral | None | None | None | None | I |
| R/W | 0.8947 | likely_pathogenic | 0.9041 | pathogenic | -0.354 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | N | 0.496576611 | None | None | I |
| R/Y | 0.9595 | likely_pathogenic | 0.9616 | pathogenic | 0.073 | Stabilizing | 0.996 | D | 0.591 | 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.