Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22151 | 66676;66677;66678 | chr2:178581918;178581917;178581916 | chr2:179446645;179446644;179446643 |
| N2AB | 20510 | 61753;61754;61755 | chr2:178581918;178581917;178581916 | chr2:179446645;179446644;179446643 |
| N2A | 19583 | 58972;58973;58974 | chr2:178581918;178581917;178581916 | chr2:179446645;179446644;179446643 |
| N2B | 13086 | 39481;39482;39483 | chr2:178581918;178581917;178581916 | chr2:179446645;179446644;179446643 |
| Novex-1 | 13211 | 39856;39857;39858 | chr2:178581918;178581917;178581916 | chr2:179446645;179446644;179446643 |
| Novex-2 | 13278 | 40057;40058;40059 | chr2:178581918;178581917;178581916 | chr2:179446645;179446644;179446643 |
| 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/L | None | None | None | N | 0.04 | 0.064 | 0.238705975628 | gnomAD-4.0.0 | 6.8453E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.1599E-05 | 0 |
| R/P | rs781750042  |
0.099 | 0.076 | N | 0.493 | 0.088 | 0.185906805712 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/P | rs781750042 |
0.099 | 0.076 | N | 0.493 | 0.088 | 0.185906805712 | gnomAD-4.0.0 | 2.05359E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79946E-06 | 1.15988E-05 | 0 |
| R/Q | rs781750042 |
0.277 | None | N | 0.043 | 0.1 | 0.0986583533028 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/Q | rs781750042 |
0.277 | None | N | 0.043 | 0.1 | 0.0986583533028 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs781750042 |
0.277 | None | N | 0.043 | 0.1 | 0.0986583533028 | gnomAD-4.0.0 | 4.3399E-06 | None | None | None | None | N | None | 2.67165E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39146E-06 | 0 | 1.602E-05 |
| R/W | rs748238939 |
-0.282 | 0.88 | N | 0.247 | 0.244 | 0.417081434665 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 9.8E-05 | None | 0 | 0 | 0 |
| R/W | rs748238939 |
-0.282 | 0.88 | N | 0.247 | 0.244 | 0.417081434665 | gnomAD-4.0.0 | 1.02678E-05 | None | None | None | None | N | None | 1.19689E-04 | 2.23834E-05 | None | 0 | 0 | None | 0 | 0 | 8.99727E-07 | 1.04391E-04 | 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 | 0.2598 | likely_benign | 0.2806 | benign | -0.243 | Destabilizing | 0.002 | N | 0.195 | neutral | None | None | None | None | N |
| R/C | 0.1199 | likely_benign | 0.1255 | benign | -0.173 | Destabilizing | 0.314 | N | 0.281 | neutral | None | None | None | None | N |
| R/D | 0.6172 | likely_pathogenic | 0.6701 | pathogenic | 0.113 | Stabilizing | 0.021 | N | 0.45 | neutral | None | None | None | None | N |
| R/E | 0.2657 | likely_benign | 0.2781 | benign | 0.228 | Stabilizing | 0.004 | N | 0.176 | neutral | None | None | None | None | N |
| R/F | 0.3843 | ambiguous | 0.4299 | ambiguous | -0.135 | Destabilizing | 0.01 | N | 0.529 | neutral | None | None | None | None | N |
| R/G | 0.251 | likely_benign | 0.2829 | benign | -0.537 | Destabilizing | 0.016 | N | 0.332 | neutral | N | 0.48486766 | None | None | N |
| R/H | 0.0966 | likely_benign | 0.106 | benign | -1.036 | Destabilizing | 0.069 | N | 0.205 | neutral | None | None | None | None | N |
| R/I | 0.1623 | likely_benign | 0.1836 | benign | 0.529 | Stabilizing | 0.002 | N | 0.345 | neutral | None | None | None | None | N |
| R/K | 0.0879 | likely_benign | 0.0865 | benign | -0.23 | Destabilizing | None | N | 0.04 | neutral | None | None | None | None | N |
| R/L | 0.1446 | likely_benign | 0.164 | benign | 0.529 | Stabilizing | None | N | 0.04 | neutral | N | 0.463817598 | None | None | N |
| R/M | 0.1896 | likely_benign | 0.2139 | benign | 0.064 | Stabilizing | 0.001 | N | 0.249 | neutral | None | None | None | None | N |
| R/N | 0.4346 | ambiguous | 0.4919 | ambiguous | 0.197 | Stabilizing | 0.021 | N | 0.272 | neutral | None | None | None | None | N |
| R/P | 0.9183 | likely_pathogenic | 0.9324 | pathogenic | 0.294 | Stabilizing | 0.076 | N | 0.493 | neutral | N | 0.482982149 | None | None | N |
| R/Q | 0.0854 | likely_benign | 0.0799 | benign | 0.097 | Stabilizing | None | N | 0.043 | neutral | N | 0.451869808 | None | None | N |
| R/S | 0.3357 | likely_benign | 0.3661 | ambiguous | -0.357 | Destabilizing | 0.004 | N | 0.257 | neutral | None | None | None | None | N |
| R/T | 0.1685 | likely_benign | 0.1861 | benign | -0.068 | Destabilizing | 0.009 | N | 0.27 | neutral | None | None | None | None | N |
| R/V | 0.1925 | likely_benign | 0.2012 | benign | 0.294 | Stabilizing | None | N | 0.067 | neutral | None | None | None | None | N |
| R/W | 0.1751 | likely_benign | 0.2083 | benign | 0.033 | Stabilizing | 0.88 | D | 0.247 | neutral | N | 0.4946376 | None | None | N |
| R/Y | 0.3061 | likely_benign | 0.3352 | benign | 0.374 | Stabilizing | 0.041 | N | 0.459 | 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.