Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31966 | 96121;96122;96123 | chr2:178544333;178544332;178544331 | chr2:179409060;179409059;179409058 |
| N2AB | 30325 | 91198;91199;91200 | chr2:178544333;178544332;178544331 | chr2:179409060;179409059;179409058 |
| N2A | 29398 | 88417;88418;88419 | chr2:178544333;178544332;178544331 | chr2:179409060;179409059;179409058 |
| N2B | 22901 | 68926;68927;68928 | chr2:178544333;178544332;178544331 | chr2:179409060;179409059;179409058 |
| Novex-1 | 23026 | 69301;69302;69303 | chr2:178544333;178544332;178544331 | chr2:179409060;179409059;179409058 |
| Novex-2 | 23093 | 69502;69503;69504 | chr2:178544333;178544332;178544331 | chr2:179409060;179409059;179409058 |
| 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/I | rs772097745  |
0.336 | 0.947 | N | 0.613 | 0.299 | 0.51469891142 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| R/I | rs772097745 |
0.336 | 0.947 | N | 0.613 | 0.299 | 0.51469891142 | gnomAD-4.0.0 | 1.59138E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.88274E-05 | 0 | 0 | 0 | 0 |
| R/K | None | 0.091 | 0.028 | N | 0.206 | 0.197 | 0.149567049428 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/K | None | 0.091 | 0.028 | N | 0.206 | 0.197 | 0.149567049428 | gnomAD-4.0.0 | 7.95692E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85863E-06 | 5.73099E-05 | 0 |
| R/T | rs772097745 |
0.005 | 0.028 | N | 0.268 | 0.212 | 0.356690202451 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/T | rs772097745 |
0.005 | 0.028 | N | 0.268 | 0.212 | 0.356690202451 | gnomAD-4.0.0 | 1.59138E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-05 | 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 | 0.3636 | ambiguous | 0.4315 | ambiguous | -0.009 | Destabilizing | 0.737 | D | 0.471 | neutral | None | None | None | None | I |
| R/C | 0.1714 | likely_benign | 0.1885 | benign | -0.218 | Destabilizing | 0.998 | D | 0.535 | neutral | None | None | None | None | I |
| R/D | 0.6312 | likely_pathogenic | 0.6984 | pathogenic | -0.2 | Destabilizing | 0.932 | D | 0.617 | neutral | None | None | None | None | I |
| R/E | 0.3562 | ambiguous | 0.4087 | ambiguous | -0.158 | Destabilizing | 0.737 | D | 0.499 | neutral | None | None | None | None | I |
| R/F | 0.5278 | ambiguous | 0.5996 | pathogenic | -0.302 | Destabilizing | 0.98 | D | 0.577 | neutral | None | None | None | None | I |
| R/G | 0.2184 | likely_benign | 0.2582 | benign | -0.16 | Destabilizing | 0.912 | D | 0.571 | neutral | N | 0.440346092 | None | None | I |
| R/H | 0.1133 | likely_benign | 0.1287 | benign | -0.574 | Destabilizing | 0.047 | N | 0.267 | neutral | None | None | None | None | I |
| R/I | 0.2928 | likely_benign | 0.327 | benign | 0.345 | Stabilizing | 0.947 | D | 0.613 | neutral | N | 0.466167256 | None | None | I |
| R/K | 0.0923 | likely_benign | 0.1014 | benign | -0.126 | Destabilizing | 0.028 | N | 0.206 | neutral | N | 0.398902114 | None | None | I |
| R/L | 0.2636 | likely_benign | 0.3076 | benign | 0.345 | Stabilizing | 0.872 | D | 0.571 | neutral | None | None | None | None | I |
| R/M | 0.3012 | likely_benign | 0.341 | ambiguous | -0.031 | Destabilizing | 0.993 | D | 0.587 | neutral | None | None | None | None | I |
| R/N | 0.5199 | ambiguous | 0.6002 | pathogenic | 0.036 | Stabilizing | 0.872 | D | 0.514 | neutral | None | None | None | None | I |
| R/P | 0.3965 | ambiguous | 0.4506 | ambiguous | 0.245 | Stabilizing | 0.993 | D | 0.651 | neutral | None | None | None | None | I |
| R/Q | 0.1031 | likely_benign | 0.1152 | benign | -0.053 | Destabilizing | 0.872 | D | 0.593 | neutral | None | None | None | None | I |
| R/S | 0.4366 | ambiguous | 0.5162 | ambiguous | -0.237 | Destabilizing | 0.514 | D | 0.515 | neutral | N | 0.425432568 | None | None | I |
| R/T | 0.2438 | likely_benign | 0.291 | benign | -0.083 | Destabilizing | 0.028 | N | 0.268 | neutral | N | 0.423664486 | None | None | I |
| R/V | 0.3616 | ambiguous | 0.4144 | ambiguous | 0.245 | Stabilizing | 0.872 | D | 0.609 | neutral | None | None | None | None | I |
| R/W | 0.1767 | likely_benign | 0.1883 | benign | -0.424 | Destabilizing | 0.998 | D | 0.543 | neutral | None | None | None | None | I |
| R/Y | 0.3744 | ambiguous | 0.4325 | ambiguous | -0.019 | Destabilizing | 0.96 | D | 0.621 | 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.