Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3320 | 10183;10184;10185 | chr2:178764557;178764556;178764555 | chr2:179629284;179629283;179629282 |
| N2AB | 3320 | 10183;10184;10185 | chr2:178764557;178764556;178764555 | chr2:179629284;179629283;179629282 |
| N2A | 3320 | 10183;10184;10185 | chr2:178764557;178764556;178764555 | chr2:179629284;179629283;179629282 |
| N2B | 3274 | 10045;10046;10047 | chr2:178764557;178764556;178764555 | chr2:179629284;179629283;179629282 |
| Novex-1 | 3274 | 10045;10046;10047 | chr2:178764557;178764556;178764555 | chr2:179629284;179629283;179629282 |
| Novex-2 | 3274 | 10045;10046;10047 | chr2:178764557;178764556;178764555 | chr2:179629284;179629283;179629282 |
| Novex-3 | 3320 | 10183;10184;10185 | chr2:178764557;178764556;178764555 | chr2:179629284;179629283;179629282 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs144100066  |
-1.031 | 0.928 | N | 0.641 | 0.396 | None | gnomAD-2.1.1 | 2.13E-05 | None | None | None | None | I | None | 4E-05 | 2.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.34E-05 | 1.38581E-04 |
| A/T | rs144100066 |
-1.031 | 0.928 | N | 0.641 | 0.396 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs144100066 |
-1.031 | 0.928 | N | 0.641 | 0.396 | None | gnomAD-4.0.0 | 5.57619E-06 | None | None | None | None | I | None | 4.00395E-05 | 1.66644E-05 | None | 0 | 0 | None | 0 | 0 | 2.54233E-06 | 0 | 3.20102E-05 |
| A/V | None | None | 0.039 | N | 0.341 | 0.155 | 0.376039117802 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7365 | likely_pathogenic | 0.6142 | pathogenic | -0.93 | Destabilizing | 0.998 | D | 0.758 | deleterious | None | None | None | None | I |
| A/D | 0.72 | likely_pathogenic | 0.5343 | ambiguous | -1.082 | Destabilizing | 0.996 | D | 0.838 | deleterious | N | 0.508426278 | None | None | I |
| A/E | 0.5935 | likely_pathogenic | 0.4577 | ambiguous | -1.161 | Destabilizing | 0.992 | D | 0.795 | deleterious | None | None | None | None | I |
| A/F | 0.6442 | likely_pathogenic | 0.5188 | ambiguous | -1.04 | Destabilizing | 0.983 | D | 0.848 | deleterious | None | None | None | None | I |
| A/G | 0.4118 | ambiguous | 0.324 | benign | -1.031 | Destabilizing | 0.963 | D | 0.601 | neutral | D | 0.661626638 | None | None | I |
| A/H | 0.8445 | likely_pathogenic | 0.7441 | pathogenic | -1.096 | Destabilizing | 0.999 | D | 0.826 | deleterious | None | None | None | None | I |
| A/I | 0.378 | ambiguous | 0.3016 | benign | -0.475 | Destabilizing | 0.745 | D | 0.659 | neutral | None | None | None | None | I |
| A/K | 0.8098 | likely_pathogenic | 0.7049 | pathogenic | -1.251 | Destabilizing | 0.992 | D | 0.792 | deleterious | None | None | None | None | I |
| A/L | 0.3789 | ambiguous | 0.3142 | benign | -0.475 | Destabilizing | 0.895 | D | 0.573 | neutral | None | None | None | None | I |
| A/M | 0.4202 | ambiguous | 0.3392 | benign | -0.415 | Destabilizing | 0.996 | D | 0.789 | deleterious | None | None | None | None | I |
| A/N | 0.6822 | likely_pathogenic | 0.5457 | ambiguous | -0.918 | Destabilizing | 0.997 | D | 0.848 | deleterious | None | None | None | None | I |
| A/P | 0.9574 | likely_pathogenic | 0.9695 | pathogenic | -0.555 | Destabilizing | 0.996 | D | 0.821 | deleterious | D | 0.673866721 | None | None | I |
| A/Q | 0.6555 | likely_pathogenic | 0.5279 | ambiguous | -1.145 | Destabilizing | 0.997 | D | 0.822 | deleterious | None | None | None | None | I |
| A/R | 0.7169 | likely_pathogenic | 0.5974 | pathogenic | -0.784 | Destabilizing | 0.992 | D | 0.823 | deleterious | None | None | None | None | I |
| A/S | 0.165 | likely_benign | 0.1348 | benign | -1.208 | Destabilizing | 0.928 | D | 0.618 | neutral | D | 0.532559265 | None | None | I |
| A/T | 0.1467 | likely_benign | 0.1219 | benign | -1.202 | Destabilizing | 0.928 | D | 0.641 | neutral | N | 0.508674147 | None | None | I |
| A/V | 0.159 | likely_benign | 0.1244 | benign | -0.555 | Destabilizing | 0.039 | N | 0.341 | neutral | N | 0.51050826 | None | None | I |
| A/W | 0.9616 | likely_pathogenic | 0.9239 | pathogenic | -1.286 | Destabilizing | 0.999 | D | 0.814 | deleterious | None | None | None | None | I |
| A/Y | 0.8402 | likely_pathogenic | 0.7365 | pathogenic | -0.932 | Destabilizing | 0.992 | D | 0.84 | deleterious | None | None | None | None | I |
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.