Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29307 | 88144;88145;88146 | chr2:178557343;178557342;178557341 | chr2:179422070;179422069;179422068 |
| N2AB | 27666 | 83221;83222;83223 | chr2:178557343;178557342;178557341 | chr2:179422070;179422069;179422068 |
| N2A | 26739 | 80440;80441;80442 | chr2:178557343;178557342;178557341 | chr2:179422070;179422069;179422068 |
| N2B | 20242 | 60949;60950;60951 | chr2:178557343;178557342;178557341 | chr2:179422070;179422069;179422068 |
| Novex-1 | 20367 | 61324;61325;61326 | chr2:178557343;178557342;178557341 | chr2:179422070;179422069;179422068 |
| Novex-2 | 20434 | 61525;61526;61527 | chr2:178557343;178557342;178557341 | chr2:179422070;179422069;179422068 |
| 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/F | None | None | 0.901 | N | 0.575 | 0.23 | 0.531972677126 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/T | rs1332665618  |
-2.106 | 0.722 | N | 0.575 | 0.322 | 0.574366754605 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| I/T | rs1332665618 |
-2.106 | 0.722 | N | 0.575 | 0.322 | 0.574366754605 | gnomAD-4.0.0 | 3.182E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71553E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5732 | likely_pathogenic | 0.5751 | pathogenic | -2.379 | Highly Destabilizing | 0.044 | N | 0.299 | neutral | None | None | None | None | N |
| I/C | 0.7961 | likely_pathogenic | 0.8128 | pathogenic | -1.342 | Destabilizing | 0.989 | D | 0.657 | neutral | None | None | None | None | N |
| I/D | 0.9058 | likely_pathogenic | 0.9124 | pathogenic | -2.388 | Highly Destabilizing | 0.961 | D | 0.757 | deleterious | None | None | None | None | N |
| I/E | 0.782 | likely_pathogenic | 0.7686 | pathogenic | -2.241 | Highly Destabilizing | 0.961 | D | 0.742 | deleterious | None | None | None | None | N |
| I/F | 0.3348 | likely_benign | 0.3361 | benign | -1.465 | Destabilizing | 0.901 | D | 0.575 | neutral | N | 0.446618703 | None | None | N |
| I/G | 0.8495 | likely_pathogenic | 0.8639 | pathogenic | -2.846 | Highly Destabilizing | 0.923 | D | 0.685 | prob.neutral | None | None | None | None | N |
| I/H | 0.78 | likely_pathogenic | 0.7742 | pathogenic | -2.216 | Highly Destabilizing | 0.996 | D | 0.76 | deleterious | None | None | None | None | N |
| I/K | 0.7589 | likely_pathogenic | 0.7563 | pathogenic | -1.755 | Destabilizing | 0.961 | D | 0.744 | deleterious | None | None | None | None | N |
| I/L | 0.1428 | likely_benign | 0.1546 | benign | -1.063 | Destabilizing | 0.19 | N | 0.317 | neutral | N | 0.442423605 | None | None | N |
| I/M | 0.1564 | likely_benign | 0.1613 | benign | -0.77 | Destabilizing | 0.901 | D | 0.553 | neutral | N | 0.425339354 | None | None | N |
| I/N | 0.5465 | ambiguous | 0.5422 | ambiguous | -1.833 | Destabilizing | 0.983 | D | 0.777 | deleterious | N | 0.448482786 | None | None | N |
| I/P | 0.8473 | likely_pathogenic | 0.8612 | pathogenic | -1.479 | Destabilizing | 0.961 | D | 0.772 | deleterious | None | None | None | None | N |
| I/Q | 0.6675 | likely_pathogenic | 0.6531 | pathogenic | -1.829 | Destabilizing | 0.987 | D | 0.777 | deleterious | None | None | None | None | N |
| I/R | 0.6631 | likely_pathogenic | 0.6543 | pathogenic | -1.299 | Destabilizing | 0.961 | D | 0.775 | deleterious | None | None | None | None | N |
| I/S | 0.503 | ambiguous | 0.5091 | ambiguous | -2.496 | Highly Destabilizing | 0.565 | D | 0.647 | neutral | N | 0.396651243 | None | None | N |
| I/T | 0.4742 | ambiguous | 0.4762 | ambiguous | -2.228 | Highly Destabilizing | 0.722 | D | 0.575 | neutral | N | 0.392802861 | None | None | N |
| I/V | 0.1432 | likely_benign | 0.1482 | benign | -1.479 | Destabilizing | 0.003 | N | 0.151 | neutral | N | 0.422741766 | None | None | N |
| I/W | 0.9042 | likely_pathogenic | 0.9126 | pathogenic | -1.807 | Destabilizing | 0.996 | D | 0.755 | deleterious | None | None | None | None | N |
| I/Y | 0.7262 | likely_pathogenic | 0.7152 | pathogenic | -1.544 | Destabilizing | 0.961 | D | 0.683 | prob.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.