Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20633 | 62122;62123;62124 | chr2:178589828;178589827;178589826 | chr2:179454555;179454554;179454553 |
| N2AB | 18992 | 57199;57200;57201 | chr2:178589828;178589827;178589826 | chr2:179454555;179454554;179454553 |
| N2A | 18065 | 54418;54419;54420 | chr2:178589828;178589827;178589826 | chr2:179454555;179454554;179454553 |
| N2B | 11568 | 34927;34928;34929 | chr2:178589828;178589827;178589826 | chr2:179454555;179454554;179454553 |
| Novex-1 | 11693 | 35302;35303;35304 | chr2:178589828;178589827;178589826 | chr2:179454555;179454554;179454553 |
| Novex-2 | 11760 | 35503;35504;35505 | chr2:178589828;178589827;178589826 | chr2:179454555;179454554;179454553 |
| 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/S | rs1227248928  |
-3.39 | 0.549 | N | 0.599 | 0.153 | 0.634365452782 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| L/S | rs1227248928 |
-3.39 | 0.549 | N | 0.599 | 0.153 | 0.634365452782 | gnomAD-4.0.0 | 6.15877E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.09623E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.2617 | likely_benign | 0.222 | benign | -1.52 | Destabilizing | 0.25 | N | 0.537 | neutral | None | None | None | None | N |
| L/C | 0.6996 | likely_pathogenic | 0.62 | pathogenic | -0.818 | Destabilizing | 0.992 | D | 0.585 | neutral | None | None | None | None | N |
| L/D | 0.723 | likely_pathogenic | 0.6492 | pathogenic | -0.86 | Destabilizing | 0.85 | D | 0.633 | neutral | None | None | None | None | N |
| L/E | 0.4188 | ambiguous | 0.3537 | ambiguous | -0.868 | Destabilizing | 0.447 | N | 0.647 | neutral | None | None | None | None | N |
| L/F | 0.2653 | likely_benign | 0.2083 | benign | -1.114 | Destabilizing | 0.81 | D | 0.617 | neutral | N | 0.434710986 | None | None | N |
| L/G | 0.6444 | likely_pathogenic | 0.5516 | ambiguous | -1.826 | Destabilizing | 0.617 | D | 0.639 | neutral | None | None | None | None | N |
| L/H | 0.3901 | ambiguous | 0.3193 | benign | -0.943 | Destabilizing | 0.977 | D | 0.604 | neutral | None | None | None | None | N |
| L/I | 0.1046 | likely_benign | 0.0948 | benign | -0.762 | Destabilizing | 0.002 | N | 0.159 | neutral | N | 0.347996078 | None | None | N |
| L/K | 0.4041 | ambiguous | 0.3319 | benign | -0.945 | Destabilizing | 0.447 | N | 0.588 | neutral | None | None | None | None | N |
| L/M | 0.1401 | likely_benign | 0.1347 | benign | -0.561 | Destabilizing | 0.059 | N | 0.222 | neutral | None | None | None | None | N |
| L/N | 0.3884 | ambiguous | 0.3245 | benign | -0.734 | Destabilizing | 0.85 | D | 0.634 | neutral | None | None | None | None | N |
| L/P | 0.5877 | likely_pathogenic | 0.5081 | ambiguous | -0.983 | Destabilizing | 0.92 | D | 0.638 | neutral | None | None | None | None | N |
| L/Q | 0.2025 | likely_benign | 0.1796 | benign | -0.913 | Destabilizing | 0.85 | D | 0.617 | neutral | None | None | None | None | N |
| L/R | 0.4178 | ambiguous | 0.3372 | benign | -0.326 | Destabilizing | 0.005 | N | 0.5 | neutral | None | None | None | None | N |
| L/S | 0.3331 | likely_benign | 0.2498 | benign | -1.333 | Destabilizing | 0.549 | D | 0.599 | neutral | N | 0.422549765 | None | None | N |
| L/T | 0.2323 | likely_benign | 0.192 | benign | -1.218 | Destabilizing | 0.617 | D | 0.565 | neutral | None | None | None | None | N |
| L/V | 0.1155 | likely_benign | 0.1063 | benign | -0.983 | Destabilizing | 0.002 | N | 0.179 | neutral | N | 0.37666276 | None | None | N |
| L/W | 0.5806 | likely_pathogenic | 0.4398 | ambiguous | -1.159 | Destabilizing | 0.992 | D | 0.596 | neutral | None | None | None | None | N |
| L/Y | 0.5657 | likely_pathogenic | 0.4492 | ambiguous | -0.941 | Destabilizing | 0.972 | D | 0.635 | 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.