Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35740 | 107443;107444;107445 | chr2:178528533;178528532;178528531 | chr2:179393260;179393259;179393258 |
| N2AB | 34099 | 102520;102521;102522 | chr2:178528533;178528532;178528531 | chr2:179393260;179393259;179393258 |
| N2A | 33172 | 99739;99740;99741 | chr2:178528533;178528532;178528531 | chr2:179393260;179393259;179393258 |
| N2B | 26675 | 80248;80249;80250 | chr2:178528533;178528532;178528531 | chr2:179393260;179393259;179393258 |
| Novex-1 | 26800 | 80623;80624;80625 | chr2:178528533;178528532;178528531 | chr2:179393260;179393259;179393258 |
| Novex-2 | 26867 | 80824;80825;80826 | chr2:178528533;178528532;178528531 | chr2:179393260;179393259;179393258 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | None | None | 0.301 | N | 0.4 | 0.27 | 0.695163590071 | gnomAD-4.0.0 | 1.20037E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31255E-06 | 0 | 0 |
| L/V | rs1176056991  |
-0.342 | 0.019 | N | 0.187 | 0.053 | 0.170165803431 | gnomAD-2.1.1 | 8.26E-06 | None | None | None | None | N | None | 0 | 5.98E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/V | rs1176056991 |
-0.342 | 0.019 | N | 0.187 | 0.053 | 0.170165803431 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | rs1176056991 |
-0.342 | 0.019 | N | 0.187 | 0.053 | 0.170165803431 | gnomAD-4.0.0 | 1.87044E-06 | None | None | None | None | N | None | 0 | 5.09061E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.2746 | likely_benign | 0.2488 | benign | -0.989 | Destabilizing | 0.002 | N | 0.177 | neutral | None | None | None | None | N |
| L/C | 0.6232 | likely_pathogenic | 0.6354 | pathogenic | -0.699 | Destabilizing | 0.859 | D | 0.286 | neutral | None | None | None | None | N |
| L/D | 0.6519 | likely_pathogenic | 0.6043 | pathogenic | -0.433 | Destabilizing | 0.22 | N | 0.392 | neutral | None | None | None | None | N |
| L/E | 0.2941 | likely_benign | 0.2645 | benign | -0.486 | Destabilizing | 0.055 | N | 0.333 | neutral | None | None | None | None | N |
| L/F | 0.1678 | likely_benign | 0.1513 | benign | -0.774 | Destabilizing | 0.22 | N | 0.246 | neutral | None | None | None | None | N |
| L/G | 0.6525 | likely_pathogenic | 0.6052 | pathogenic | -1.216 | Destabilizing | 0.124 | N | 0.354 | neutral | None | None | None | None | N |
| L/H | 0.2055 | likely_benign | 0.1892 | benign | -0.4 | Destabilizing | 0.002 | N | 0.276 | neutral | None | None | None | None | N |
| L/I | 0.0923 | likely_benign | 0.0891 | benign | -0.485 | Destabilizing | 0.001 | N | 0.213 | neutral | None | None | None | None | N |
| L/K | 0.2469 | likely_benign | 0.2122 | benign | -0.645 | Destabilizing | 0.004 | N | 0.218 | neutral | None | None | None | None | N |
| L/M | 0.1134 | likely_benign | 0.1131 | benign | -0.476 | Destabilizing | 0.003 | N | 0.229 | neutral | N | 0.469624141 | None | None | N |
| L/N | 0.3545 | ambiguous | 0.3081 | benign | -0.465 | Destabilizing | 0.124 | N | 0.411 | neutral | None | None | None | None | N |
| L/P | 0.9476 | likely_pathogenic | 0.9282 | pathogenic | -0.619 | Destabilizing | 0.301 | N | 0.4 | neutral | N | 0.483237248 | None | None | N |
| L/Q | 0.1209 | likely_benign | 0.1114 | benign | -0.658 | Destabilizing | 0.001 | N | 0.199 | neutral | N | 0.428601451 | None | None | N |
| L/R | 0.1957 | likely_benign | 0.1701 | benign | -0.052 | Destabilizing | 0.096 | N | 0.379 | neutral | N | 0.420368757 | None | None | N |
| L/S | 0.2374 | likely_benign | 0.2089 | benign | -0.967 | Destabilizing | 0.055 | N | 0.315 | neutral | None | None | None | None | N |
| L/T | 0.2114 | likely_benign | 0.1899 | benign | -0.906 | Destabilizing | 0.104 | N | 0.311 | neutral | None | None | None | None | N |
| L/V | 0.1094 | likely_benign | 0.1078 | benign | -0.619 | Destabilizing | 0.019 | N | 0.187 | neutral | N | 0.45886843 | None | None | N |
| L/W | 0.3933 | ambiguous | 0.3629 | ambiguous | -0.808 | Destabilizing | 0.958 | D | 0.321 | neutral | None | None | None | None | N |
| L/Y | 0.3812 | ambiguous | 0.3531 | ambiguous | -0.579 | Destabilizing | 0.124 | N | 0.38 | neutral | 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.