Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19878 | 59857;59858;59859 | chr2:178592272;178592271;178592270 | chr2:179456999;179456998;179456997 |
| N2AB | 18237 | 54934;54935;54936 | chr2:178592272;178592271;178592270 | chr2:179456999;179456998;179456997 |
| N2A | 17310 | 52153;52154;52155 | chr2:178592272;178592271;178592270 | chr2:179456999;179456998;179456997 |
| N2B | 10813 | 32662;32663;32664 | chr2:178592272;178592271;178592270 | chr2:179456999;179456998;179456997 |
| Novex-1 | 10938 | 33037;33038;33039 | chr2:178592272;178592271;178592270 | chr2:179456999;179456998;179456997 |
| Novex-2 | 11005 | 33238;33239;33240 | chr2:178592272;178592271;178592270 | chr2:179456999;179456998;179456997 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs752854931  |
None | 1.0 | D | 0.743 | 0.726 | 0.739926861457 | gnomAD-4.0.0 | 1.60234E-06 | None | None | None | None | N | None | 0 | 2.33165E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | rs752854931 |
-2.23 | 1.0 | D | 0.753 | 0.729 | 0.758584903254 | gnomAD-2.1.1 | 4.15E-06 | None | None | None | None | N | None | 0 | 3E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/T | rs752854931 |
-2.23 | 1.0 | D | 0.753 | 0.729 | 0.758584903254 | gnomAD-4.0.0 | 3.20467E-06 | None | None | None | None | N | None | 0 | 2.33165E-05 | None | 0 | 2.79673E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.8794 | likely_pathogenic | 0.8804 | pathogenic | -1.724 | Destabilizing | 0.999 | D | 0.803 | deleterious | D | 0.625395733 | None | None | N |
| P/C | 0.9912 | likely_pathogenic | 0.9915 | pathogenic | -2.023 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| P/D | 0.9991 | likely_pathogenic | 0.9993 | pathogenic | -3.438 | Highly Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| P/E | 0.9979 | likely_pathogenic | 0.9985 | pathogenic | -3.34 | Highly Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| P/F | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -1.02 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| P/G | 0.9931 | likely_pathogenic | 0.9942 | pathogenic | -2.075 | Highly Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| P/H | 0.9983 | likely_pathogenic | 0.9985 | pathogenic | -1.545 | Destabilizing | 1.0 | D | 0.775 | deleterious | D | 0.658039868 | None | None | N |
| P/I | 0.991 | likely_pathogenic | 0.993 | pathogenic | -0.79 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| P/K | 0.9988 | likely_pathogenic | 0.9992 | pathogenic | -1.62 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| P/L | 0.9789 | likely_pathogenic | 0.9835 | pathogenic | -0.79 | Destabilizing | 1.0 | D | 0.83 | deleterious | D | 0.632532116 | None | None | N |
| P/M | 0.9963 | likely_pathogenic | 0.9969 | pathogenic | -1.092 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| P/N | 0.9991 | likely_pathogenic | 0.9993 | pathogenic | -1.981 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| P/Q | 0.9975 | likely_pathogenic | 0.9981 | pathogenic | -2.047 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| P/R | 0.9958 | likely_pathogenic | 0.9971 | pathogenic | -1.219 | Destabilizing | 1.0 | D | 0.825 | deleterious | D | 0.657838063 | None | None | N |
| P/S | 0.99 | likely_pathogenic | 0.99 | pathogenic | -2.297 | Highly Destabilizing | 1.0 | D | 0.743 | deleterious | D | 0.657636259 | None | None | N |
| P/T | 0.9837 | likely_pathogenic | 0.9866 | pathogenic | -2.099 | Highly Destabilizing | 1.0 | D | 0.753 | deleterious | D | 0.657838063 | None | None | N |
| P/V | 0.9693 | likely_pathogenic | 0.9759 | pathogenic | -1.076 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| P/W | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -1.434 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| P/Y | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -1.141 | Destabilizing | 1.0 | D | 0.842 | 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.