Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20822 | 62689;62690;62691 | chr2:178589261;178589260;178589259 | chr2:179453988;179453987;179453986 |
| N2AB | 19181 | 57766;57767;57768 | chr2:178589261;178589260;178589259 | chr2:179453988;179453987;179453986 |
| N2A | 18254 | 54985;54986;54987 | chr2:178589261;178589260;178589259 | chr2:179453988;179453987;179453986 |
| N2B | 11757 | 35494;35495;35496 | chr2:178589261;178589260;178589259 | chr2:179453988;179453987;179453986 |
| Novex-1 | 11882 | 35869;35870;35871 | chr2:178589261;178589260;178589259 | chr2:179453988;179453987;179453986 |
| Novex-2 | 11949 | 36070;36071;36072 | chr2:178589261;178589260;178589259 | chr2:179453988;179453987;179453986 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.977 | D | 0.622 | 0.289 | 0.356281029322 | gnomAD-4.0.0 | 1.59191E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02499E-05 |
| T/S | rs376352599  |
-0.357 | 0.955 | N | 0.619 | 0.225 | 0.319970858106 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 1.29232E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs376352599 |
-0.357 | 0.955 | N | 0.619 | 0.225 | 0.319970858106 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| T/S | rs376352599 |
-0.357 | 0.955 | N | 0.619 | 0.225 | 0.319970858106 | gnomAD-4.0.0 | 2.10742E-05 | None | None | None | None | N | None | 1.33518E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.7127E-05 | 0 | 1.60154E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1158 | likely_benign | 0.1025 | benign | -0.498 | Destabilizing | 0.977 | D | 0.622 | neutral | D | 0.523455839 | None | None | N |
| T/C | 0.4008 | ambiguous | 0.412 | ambiguous | -0.215 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| T/D | 0.4902 | ambiguous | 0.4364 | ambiguous | 0.197 | Stabilizing | 0.99 | D | 0.694 | prob.neutral | None | None | None | None | N |
| T/E | 0.469 | ambiguous | 0.4212 | ambiguous | 0.126 | Stabilizing | 0.995 | D | 0.685 | prob.neutral | None | None | None | None | N |
| T/F | 0.3303 | likely_benign | 0.2933 | benign | -0.942 | Destabilizing | 0.999 | D | 0.806 | deleterious | None | None | None | None | N |
| T/G | 0.251 | likely_benign | 0.2303 | benign | -0.645 | Destabilizing | 0.966 | D | 0.704 | prob.neutral | None | None | None | None | N |
| T/H | 0.317 | likely_benign | 0.2527 | benign | -1.005 | Destabilizing | 0.999 | D | 0.809 | deleterious | None | None | None | None | N |
| T/I | 0.2233 | likely_benign | 0.2101 | benign | -0.226 | Destabilizing | 0.997 | D | 0.753 | deleterious | D | 0.535078342 | None | None | N |
| T/K | 0.3507 | ambiguous | 0.2673 | benign | -0.363 | Destabilizing | 0.995 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/L | 0.1487 | likely_benign | 0.129 | benign | -0.226 | Destabilizing | 0.991 | D | 0.667 | neutral | None | None | None | None | N |
| T/M | 0.1281 | likely_benign | 0.1208 | benign | 0.112 | Stabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| T/N | 0.1225 | likely_benign | 0.1005 | benign | -0.117 | Destabilizing | 0.235 | N | 0.336 | neutral | N | 0.454038613 | None | None | N |
| T/P | 0.2477 | likely_benign | 0.1974 | benign | -0.288 | Destabilizing | 0.999 | D | 0.751 | deleterious | N | 0.487365078 | None | None | N |
| T/Q | 0.307 | likely_benign | 0.254 | benign | -0.386 | Destabilizing | 0.998 | D | 0.762 | deleterious | None | None | None | None | N |
| T/R | 0.3162 | likely_benign | 0.2256 | benign | -0.104 | Destabilizing | 0.995 | D | 0.755 | deleterious | None | None | None | None | N |
| T/S | 0.1063 | likely_benign | 0.0968 | benign | -0.377 | Destabilizing | 0.955 | D | 0.619 | neutral | N | 0.475664679 | None | None | N |
| T/V | 0.1634 | likely_benign | 0.158 | benign | -0.288 | Destabilizing | 0.991 | D | 0.669 | neutral | None | None | None | None | N |
| T/W | 0.7351 | likely_pathogenic | 0.6744 | pathogenic | -0.894 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| T/Y | 0.3848 | ambiguous | 0.3164 | benign | -0.628 | Destabilizing | 0.999 | D | 0.804 | deleterious | 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.