Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31494 | 94705;94706;94707 | chr2:178547045;178547044;178547043 | chr2:179411772;179411771;179411770 |
| N2AB | 29853 | 89782;89783;89784 | chr2:178547045;178547044;178547043 | chr2:179411772;179411771;179411770 |
| N2A | 28926 | 87001;87002;87003 | chr2:178547045;178547044;178547043 | chr2:179411772;179411771;179411770 |
| N2B | 22429 | 67510;67511;67512 | chr2:178547045;178547044;178547043 | chr2:179411772;179411771;179411770 |
| Novex-1 | 22554 | 67885;67886;67887 | chr2:178547045;178547044;178547043 | chr2:179411772;179411771;179411770 |
| Novex-2 | 22621 | 68086;68087;68088 | chr2:178547045;178547044;178547043 | chr2:179411772;179411771;179411770 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | rs748231785  |
-1.644 | 0.997 | N | 0.739 | 0.472 | 0.575848135552 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/D | rs748231785 |
-1.644 | 0.997 | N | 0.739 | 0.472 | 0.575848135552 | gnomAD-4.0.0 | 3.18423E-06 | None | None | None | None | I | None | 0 | 4.5731E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs769948504 |
-1.252 | 0.977 | N | 0.608 | 0.184 | 0.37097340754 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| A/T | rs769948504 |
-1.252 | 0.977 | N | 0.608 | 0.184 | 0.37097340754 | gnomAD-4.0.0 | 5.4749E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 8.11726E-05 | 1.65684E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6039 | likely_pathogenic | 0.5657 | pathogenic | -0.946 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| A/D | 0.9351 | likely_pathogenic | 0.9313 | pathogenic | -0.83 | Destabilizing | 0.997 | D | 0.739 | prob.delet. | N | 0.48329084 | None | None | I |
| A/E | 0.8346 | likely_pathogenic | 0.8318 | pathogenic | -0.899 | Destabilizing | 0.995 | D | 0.695 | prob.neutral | None | None | None | None | I |
| A/F | 0.7533 | likely_pathogenic | 0.7656 | pathogenic | -1.182 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | I |
| A/G | 0.2916 | likely_benign | 0.2763 | benign | -1.194 | Destabilizing | 0.977 | D | 0.504 | neutral | N | 0.471681045 | None | None | I |
| A/H | 0.8991 | likely_pathogenic | 0.9009 | pathogenic | -1.129 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| A/I | 0.6393 | likely_pathogenic | 0.6249 | pathogenic | -0.629 | Destabilizing | 0.998 | D | 0.746 | deleterious | None | None | None | None | I |
| A/K | 0.9604 | likely_pathogenic | 0.9579 | pathogenic | -1.013 | Destabilizing | 0.995 | D | 0.691 | prob.neutral | None | None | None | None | I |
| A/L | 0.5582 | ambiguous | 0.5471 | ambiguous | -0.629 | Destabilizing | 0.983 | D | 0.639 | neutral | None | None | None | None | I |
| A/M | 0.538 | ambiguous | 0.5373 | ambiguous | -0.52 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| A/N | 0.7689 | likely_pathogenic | 0.7715 | pathogenic | -0.704 | Destabilizing | 0.998 | D | 0.803 | deleterious | None | None | None | None | I |
| A/P | 0.1106 | likely_benign | 0.1061 | benign | -0.713 | Destabilizing | 0.117 | N | 0.379 | neutral | N | 0.367170911 | None | None | I |
| A/Q | 0.7883 | likely_pathogenic | 0.7792 | pathogenic | -0.94 | Destabilizing | 0.998 | D | 0.782 | deleterious | None | None | None | None | I |
| A/R | 0.9416 | likely_pathogenic | 0.9384 | pathogenic | -0.6 | Destabilizing | 0.998 | D | 0.767 | deleterious | None | None | None | None | I |
| A/S | 0.2045 | likely_benign | 0.2108 | benign | -1.099 | Destabilizing | 0.977 | D | 0.535 | neutral | N | 0.499871611 | None | None | I |
| A/T | 0.36 | ambiguous | 0.3749 | ambiguous | -1.079 | Destabilizing | 0.977 | D | 0.608 | neutral | N | 0.513051552 | None | None | I |
| A/V | 0.3459 | ambiguous | 0.3321 | benign | -0.713 | Destabilizing | 0.989 | D | 0.559 | neutral | N | 0.50014097 | None | None | I |
| A/W | 0.9616 | likely_pathogenic | 0.9645 | pathogenic | -1.367 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | I |
| A/Y | 0.8544 | likely_pathogenic | 0.8657 | pathogenic | -1.019 | Destabilizing | 1.0 | D | 0.819 | 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.