Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32357 | 97294;97295;97296 | chr2:178542785;178542784;178542783 | chr2:179407512;179407511;179407510 |
| N2AB | 30716 | 92371;92372;92373 | chr2:178542785;178542784;178542783 | chr2:179407512;179407511;179407510 |
| N2A | 29789 | 89590;89591;89592 | chr2:178542785;178542784;178542783 | chr2:179407512;179407511;179407510 |
| N2B | 23292 | 70099;70100;70101 | chr2:178542785;178542784;178542783 | chr2:179407512;179407511;179407510 |
| Novex-1 | 23417 | 70474;70475;70476 | chr2:178542785;178542784;178542783 | chr2:179407512;179407511;179407510 |
| Novex-2 | 23484 | 70675;70676;70677 | chr2:178542785;178542784;178542783 | chr2:179407512;179407511;179407510 |
| 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/I | rs375538626  |
0.187 | 0.998 | N | 0.773 | 0.348 | 0.487064551306 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.67038E-04 | None | 0 | None | 0 | 8.91E-06 | 0 |
| T/I | rs375538626 |
0.187 | 0.998 | N | 0.773 | 0.348 | 0.487064551306 | gnomAD-4.0.0 | 7.52626E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77106E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs375538626 |
-0.433 | 0.775 | N | 0.349 | 0.278 | 0.18274738541 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| T/S | rs375538626 |
-0.433 | 0.775 | N | 0.349 | 0.278 | 0.18274738541 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/S | rs375538626 |
-0.433 | 0.775 | N | 0.349 | 0.278 | 0.18274738541 | gnomAD-4.0.0 | 6.19706E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.4761E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1137 | likely_benign | 0.0969 | benign | -0.598 | Destabilizing | 0.948 | D | 0.605 | neutral | N | 0.448843437 | None | None | N |
| T/C | 0.4298 | ambiguous | 0.366 | ambiguous | -0.29 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| T/D | 0.4767 | ambiguous | 0.4133 | ambiguous | -0.207 | Destabilizing | 0.998 | D | 0.737 | prob.delet. | None | None | None | None | N |
| T/E | 0.4426 | ambiguous | 0.379 | ambiguous | -0.239 | Destabilizing | 0.998 | D | 0.743 | deleterious | None | None | None | None | N |
| T/F | 0.2853 | likely_benign | 0.2337 | benign | -0.749 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | N |
| T/G | 0.2561 | likely_benign | 0.2182 | benign | -0.823 | Destabilizing | 0.992 | D | 0.714 | prob.delet. | None | None | None | None | N |
| T/H | 0.296 | likely_benign | 0.2462 | benign | -1.144 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| T/I | 0.1991 | likely_benign | 0.1619 | benign | -0.1 | Destabilizing | 0.998 | D | 0.773 | deleterious | N | 0.479590419 | None | None | N |
| T/K | 0.2959 | likely_benign | 0.2525 | benign | -0.739 | Destabilizing | 0.998 | D | 0.743 | deleterious | None | None | None | None | N |
| T/L | 0.1183 | likely_benign | 0.1031 | benign | -0.1 | Destabilizing | 0.996 | D | 0.721 | prob.delet. | None | None | None | None | N |
| T/M | 0.0906 | likely_benign | 0.0836 | benign | 0.149 | Stabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| T/N | 0.109 | likely_benign | 0.0983 | benign | -0.513 | Destabilizing | 0.997 | D | 0.725 | prob.delet. | N | 0.442186824 | None | None | N |
| T/P | 0.1801 | likely_benign | 0.1564 | benign | -0.234 | Destabilizing | 0.998 | D | 0.77 | deleterious | N | 0.471317652 | None | None | N |
| T/Q | 0.2799 | likely_benign | 0.2446 | benign | -0.704 | Destabilizing | 0.999 | D | 0.759 | deleterious | None | None | None | None | N |
| T/R | 0.25 | likely_benign | 0.2136 | benign | -0.472 | Destabilizing | 0.999 | D | 0.77 | deleterious | None | None | None | None | N |
| T/S | 0.1254 | likely_benign | 0.108 | benign | -0.725 | Destabilizing | 0.775 | D | 0.349 | neutral | N | 0.422062268 | None | None | N |
| T/V | 0.1758 | likely_benign | 0.1429 | benign | -0.234 | Destabilizing | 0.996 | D | 0.709 | prob.delet. | None | None | None | None | N |
| T/W | 0.5976 | likely_pathogenic | 0.5511 | ambiguous | -0.726 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| T/Y | 0.2591 | likely_benign | 0.2303 | benign | -0.501 | Destabilizing | 1.0 | D | 0.783 | 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.