Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32058 | 96397;96398;96399 | chr2:178543972;178543971;178543970 | chr2:179408699;179408698;179408697 |
| N2AB | 30417 | 91474;91475;91476 | chr2:178543972;178543971;178543970 | chr2:179408699;179408698;179408697 |
| N2A | 29490 | 88693;88694;88695 | chr2:178543972;178543971;178543970 | chr2:179408699;179408698;179408697 |
| N2B | 22993 | 69202;69203;69204 | chr2:178543972;178543971;178543970 | chr2:179408699;179408698;179408697 |
| Novex-1 | 23118 | 69577;69578;69579 | chr2:178543972;178543971;178543970 | chr2:179408699;179408698;179408697 |
| Novex-2 | 23185 | 69778;69779;69780 | chr2:178543972;178543971;178543970 | chr2:179408699;179408698;179408697 |
| 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 | rs374063064  |
-0.08 | 1.0 | N | 0.733 | 0.331 | None | gnomAD-2.1.1 | 8.92E-05 | None | None | None | None | I | None | 1.24008E-04 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.5605E-04 | 1.40252E-04 |
| R/Q | rs374063064 |
-0.08 | 1.0 | N | 0.733 | 0.331 | None | gnomAD-3.1.2 | 1.31539E-04 | None | None | None | None | I | None | 1.20744E-04 | 1.31165E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.91165E-04 | 0 | 0 |
| R/Q | rs374063064 |
-0.08 | 1.0 | N | 0.733 | 0.331 | None | gnomAD-4.0.0 | 1.71673E-04 | None | None | None | None | I | None | 1.46925E-04 | 6.67E-05 | None | 3.37838E-05 | 6.68628E-05 | None | 0 | 0 | 2.09372E-04 | 1.09806E-05 | 1.60149E-04 |
| R/W | rs201463708 |
-0.628 | 1.0 | D | 0.731 | 0.442 | None | gnomAD-2.1.1 | 3.21E-05 | None | None | None | None | I | None | 1.6533E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.12E-05 | 1.40252E-04 |
| R/W | rs201463708 |
-0.628 | 1.0 | D | 0.731 | 0.442 | None | gnomAD-3.1.2 | 7.24E-05 | None | None | None | None | I | None | 1.93424E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/W | rs201463708 |
-0.628 | 1.0 | D | 0.731 | 0.442 | None | gnomAD-4.0.0 | 2.23124E-05 | None | None | None | None | I | None | 1.4702E-04 | 0 | None | 0 | 0 | None | 3.12471E-05 | 0 | 1.61057E-05 | 0 | 6.40553E-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 | 0.8971 | likely_pathogenic | 0.8994 | pathogenic | -0.846 | Destabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | I |
| R/C | 0.5649 | likely_pathogenic | 0.5486 | ambiguous | -0.83 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| R/D | 0.9423 | likely_pathogenic | 0.9393 | pathogenic | -0.03 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| R/E | 0.7837 | likely_pathogenic | 0.7758 | pathogenic | 0.073 | Stabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | I |
| R/F | 0.9396 | likely_pathogenic | 0.9393 | pathogenic | -0.933 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | I |
| R/G | 0.8364 | likely_pathogenic | 0.8217 | pathogenic | -1.115 | Destabilizing | 1.0 | D | 0.666 | neutral | N | 0.475449573 | None | None | I |
| R/H | 0.2668 | likely_benign | 0.2677 | benign | -1.458 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| R/I | 0.8207 | likely_pathogenic | 0.827 | pathogenic | -0.138 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| R/K | 0.2649 | likely_benign | 0.2649 | benign | -0.717 | Destabilizing | 0.998 | D | 0.574 | neutral | None | None | None | None | I |
| R/L | 0.7508 | likely_pathogenic | 0.7566 | pathogenic | -0.138 | Destabilizing | 1.0 | D | 0.666 | neutral | N | 0.492414965 | None | None | I |
| R/M | 0.8346 | likely_pathogenic | 0.8254 | pathogenic | -0.361 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| R/N | 0.9102 | likely_pathogenic | 0.9159 | pathogenic | -0.223 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| R/P | 0.9822 | likely_pathogenic | 0.9792 | pathogenic | -0.354 | Destabilizing | 1.0 | D | 0.67 | neutral | N | 0.495150443 | None | None | I |
| R/Q | 0.2908 | likely_benign | 0.2784 | benign | -0.45 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.492099024 | None | None | I |
| R/S | 0.9143 | likely_pathogenic | 0.9145 | pathogenic | -1.032 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| R/T | 0.7816 | likely_pathogenic | 0.7913 | pathogenic | -0.754 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| R/V | 0.8456 | likely_pathogenic | 0.8573 | pathogenic | -0.354 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| R/W | 0.5913 | likely_pathogenic | 0.5477 | ambiguous | -0.645 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | D | 0.523142973 | None | None | I |
| R/Y | 0.8225 | likely_pathogenic | 0.8175 | pathogenic | -0.307 | Destabilizing | 1.0 | D | 0.689 | prob.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.