Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19160 | 57703;57704;57705 | chr2:178597604;178597603;178597602 | chr2:179462331;179462330;179462329 |
| N2AB | 17519 | 52780;52781;52782 | chr2:178597604;178597603;178597602 | chr2:179462331;179462330;179462329 |
| N2A | 16592 | 49999;50000;50001 | chr2:178597604;178597603;178597602 | chr2:179462331;179462330;179462329 |
| N2B | 10095 | 30508;30509;30510 | chr2:178597604;178597603;178597602 | chr2:179462331;179462330;179462329 |
| Novex-1 | 10220 | 30883;30884;30885 | chr2:178597604;178597603;178597602 | chr2:179462331;179462330;179462329 |
| Novex-2 | 10287 | 31084;31085;31086 | chr2:178597604;178597603;178597602 | chr2:179462331;179462330;179462329 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | rs200778464  |
-1.099 | 0.81 | N | 0.543 | 0.304 | 0.597869843003 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/F | rs200778464 |
-1.099 | 0.81 | N | 0.543 | 0.304 | 0.597869843003 | gnomAD-4.0.0 | 6.84489E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15947E-05 | 0 |
| V/I | None | -0.351 | 0.004 | N | 0.182 | 0.039 | 0.20549828249 | gnomAD-2.1.1 | 9.28E-05 | None | None | None | None | N | None | 0 | 3.19712E-04 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-05 | 3.32779E-04 |
| V/I | None | -0.351 | 0.004 | N | 0.182 | 0.039 | 0.20549828249 | gnomAD-3.1.2 | 8.55E-05 | None | None | None | None | N | None | 2.41E-05 | 5.24178E-04 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 4.78469E-04 |
| V/I | None | -0.351 | 0.004 | N | 0.182 | 0.039 | 0.20549828249 | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 2E-03 | None | None | None | 0 | None |
| V/I | None | -0.351 | 0.004 | N | 0.182 | 0.039 | 0.20549828249 | gnomAD-4.0.0 | 5.39335E-05 | None | None | None | None | N | None | 1.33358E-05 | 3.50385E-04 | None | 0 | 0 | None | 0 | 0 | 4.9174E-05 | 0 | 1.12104E-04 |
| V/L | rs200778464 |
-0.39 | 0.002 | N | 0.181 | 0.111 | None | gnomAD-2.1.1 | 1.3965E-04 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.90137E-04 | 0 |
| V/L | rs200778464 |
-0.39 | 0.002 | N | 0.181 | 0.111 | None | gnomAD-3.1.2 | 1.84167E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 3.97176E-04 | 0 | 0 |
| V/L | rs200778464 |
-0.39 | 0.002 | N | 0.181 | 0.111 | None | gnomAD-4.0.0 | 3.04406E-04 | None | None | None | None | N | None | 5.34302E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.07803E-04 | 0 | 9.6123E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2563 | likely_benign | 0.2849 | benign | -1.497 | Destabilizing | 0.165 | N | 0.473 | neutral | N | 0.493269005 | None | None | N |
| V/C | 0.6793 | likely_pathogenic | 0.7265 | pathogenic | -1.251 | Destabilizing | 0.981 | D | 0.515 | neutral | None | None | None | None | N |
| V/D | 0.5175 | ambiguous | 0.6003 | pathogenic | -1.092 | Destabilizing | 0.773 | D | 0.599 | neutral | N | 0.5081611 | None | None | N |
| V/E | 0.3451 | ambiguous | 0.3891 | ambiguous | -1.078 | Destabilizing | 0.818 | D | 0.57 | neutral | None | None | None | None | N |
| V/F | 0.1697 | likely_benign | 0.1904 | benign | -1.236 | Destabilizing | 0.81 | D | 0.543 | neutral | N | 0.502640637 | None | None | N |
| V/G | 0.3467 | ambiguous | 0.4111 | ambiguous | -1.82 | Destabilizing | 0.773 | D | 0.585 | neutral | N | 0.498063047 | None | None | N |
| V/H | 0.5205 | ambiguous | 0.5926 | pathogenic | -1.34 | Destabilizing | 0.981 | D | 0.595 | neutral | None | None | None | None | N |
| V/I | 0.0653 | likely_benign | 0.0657 | benign | -0.706 | Destabilizing | 0.004 | N | 0.182 | neutral | N | 0.445400487 | None | None | N |
| V/K | 0.35 | ambiguous | 0.4116 | ambiguous | -1.046 | Destabilizing | 0.818 | D | 0.574 | neutral | None | None | None | None | N |
| V/L | 0.1591 | likely_benign | 0.1739 | benign | -0.706 | Destabilizing | 0.002 | N | 0.181 | neutral | N | 0.488209902 | None | None | N |
| V/M | 0.1228 | likely_benign | 0.1332 | benign | -0.635 | Destabilizing | 0.054 | N | 0.291 | neutral | None | None | None | None | N |
| V/N | 0.2819 | likely_benign | 0.3429 | ambiguous | -0.894 | Destabilizing | 0.932 | D | 0.605 | neutral | None | None | None | None | N |
| V/P | 0.7303 | likely_pathogenic | 0.7575 | pathogenic | -0.935 | Destabilizing | 0.932 | D | 0.584 | neutral | None | None | None | None | N |
| V/Q | 0.3275 | likely_benign | 0.3683 | ambiguous | -1.053 | Destabilizing | 0.818 | D | 0.591 | neutral | None | None | None | None | N |
| V/R | 0.3253 | likely_benign | 0.3855 | ambiguous | -0.621 | Destabilizing | 0.818 | D | 0.601 | neutral | None | None | None | None | N |
| V/S | 0.2818 | likely_benign | 0.3259 | benign | -1.523 | Destabilizing | 0.563 | D | 0.551 | neutral | None | None | None | None | N |
| V/T | 0.2017 | likely_benign | 0.2129 | benign | -1.389 | Destabilizing | 0.388 | N | 0.432 | neutral | None | None | None | None | N |
| V/W | 0.7558 | likely_pathogenic | 0.8201 | pathogenic | -1.384 | Destabilizing | 0.981 | D | 0.611 | neutral | None | None | None | None | N |
| V/Y | 0.4623 | ambiguous | 0.5505 | ambiguous | -1.069 | Destabilizing | 0.818 | D | 0.55 | 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.