Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30813 | 92662;92663;92664 | chr2:178549189;178549188;178549187 | chr2:179413916;179413915;179413914 |
| N2AB | 29172 | 87739;87740;87741 | chr2:178549189;178549188;178549187 | chr2:179413916;179413915;179413914 |
| N2A | 28245 | 84958;84959;84960 | chr2:178549189;178549188;178549187 | chr2:179413916;179413915;179413914 |
| N2B | 21748 | 65467;65468;65469 | chr2:178549189;178549188;178549187 | chr2:179413916;179413915;179413914 |
| Novex-1 | 21873 | 65842;65843;65844 | chr2:178549189;178549188;178549187 | chr2:179413916;179413915;179413914 |
| Novex-2 | 21940 | 66043;66044;66045 | chr2:178549189;178549188;178549187 | chr2:179413916;179413915;179413914 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs768897840  |
-2.265 | 0.971 | N | 0.593 | 0.278 | 0.5242713 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 4.44E-05 | 0 |
| I/T | rs768897840 |
-2.265 | 0.971 | N | 0.593 | 0.278 | 0.5242713 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs768897840 |
-2.265 | 0.971 | N | 0.593 | 0.278 | 0.5242713 | gnomAD-4.0.0 | 2.91268E-05 | None | None | None | None | N | None | 2.67087E-05 | 1.66761E-05 | None | 0 | 0 | None | 0 | 0 | 3.39032E-05 | 0 | 6.40512E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7098 | likely_pathogenic | 0.6913 | pathogenic | -2.327 | Highly Destabilizing | 0.855 | D | 0.581 | neutral | None | None | None | None | N |
| I/C | 0.7446 | likely_pathogenic | 0.7477 | pathogenic | -1.391 | Destabilizing | 0.998 | D | 0.602 | neutral | None | None | None | None | N |
| I/D | 0.9724 | likely_pathogenic | 0.9647 | pathogenic | -2.787 | Highly Destabilizing | 0.994 | D | 0.699 | prob.delet. | None | None | None | None | N |
| I/E | 0.9071 | likely_pathogenic | 0.8898 | pathogenic | -2.534 | Highly Destabilizing | 0.994 | D | 0.703 | prob.delet. | None | None | None | None | N |
| I/F | 0.1576 | likely_benign | 0.1706 | benign | -1.395 | Destabilizing | 0.002 | N | 0.19 | neutral | N | 0.41060948 | None | None | N |
| I/G | 0.9127 | likely_pathogenic | 0.9017 | pathogenic | -2.873 | Highly Destabilizing | 0.994 | D | 0.675 | prob.neutral | None | None | None | None | N |
| I/H | 0.7959 | likely_pathogenic | 0.7771 | pathogenic | -2.32 | Highly Destabilizing | 0.998 | D | 0.721 | deleterious | None | None | None | None | N |
| I/K | 0.8365 | likely_pathogenic | 0.8103 | pathogenic | -1.812 | Destabilizing | 0.994 | D | 0.701 | prob.delet. | None | None | None | None | N |
| I/L | 0.1293 | likely_benign | 0.1224 | benign | -0.739 | Destabilizing | 0.325 | N | 0.45 | neutral | N | 0.47479144 | None | None | N |
| I/M | 0.123 | likely_benign | 0.1244 | benign | -0.586 | Destabilizing | 0.991 | D | 0.579 | neutral | N | 0.49957526 | None | None | N |
| I/N | 0.7464 | likely_pathogenic | 0.7102 | pathogenic | -2.259 | Highly Destabilizing | 0.991 | D | 0.733 | deleterious | N | 0.4794547 | None | None | N |
| I/P | 0.9756 | likely_pathogenic | 0.9729 | pathogenic | -1.251 | Destabilizing | 0.994 | D | 0.725 | deleterious | None | None | None | None | N |
| I/Q | 0.77 | likely_pathogenic | 0.7305 | pathogenic | -2.083 | Highly Destabilizing | 0.994 | D | 0.721 | deleterious | None | None | None | None | N |
| I/R | 0.7655 | likely_pathogenic | 0.7295 | pathogenic | -1.61 | Destabilizing | 0.994 | D | 0.734 | deleterious | None | None | None | None | N |
| I/S | 0.7076 | likely_pathogenic | 0.6801 | pathogenic | -2.895 | Highly Destabilizing | 0.971 | D | 0.588 | neutral | N | 0.5071919 | None | None | N |
| I/T | 0.5797 | likely_pathogenic | 0.6621 | pathogenic | -2.493 | Highly Destabilizing | 0.971 | D | 0.593 | neutral | N | 0.4604008 | None | None | N |
| I/V | 0.1103 | likely_benign | 0.1017 | benign | -1.251 | Destabilizing | 0.49 | N | 0.432 | neutral | N | 0.37999576 | None | None | N |
| I/W | 0.7936 | likely_pathogenic | 0.8134 | pathogenic | -1.816 | Destabilizing | 0.998 | D | 0.716 | prob.delet. | None | None | None | None | N |
| I/Y | 0.5833 | likely_pathogenic | 0.5972 | pathogenic | -1.465 | Destabilizing | 0.78 | D | 0.598 | 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.