TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32046	96361;96362;96363	chr2:178544008;178544007;178544006	chr2:179408735;179408734;179408733
N2AB	30405	91438;91439;91440	chr2:178544008;178544007;178544006	chr2:179408735;179408734;179408733
N2A	29478	88657;88658;88659	chr2:178544008;178544007;178544006	chr2:179408735;179408734;179408733
N2B	22981	69166;69167;69168	chr2:178544008;178544007;178544006	chr2:179408735;179408734;179408733
Novex-1	23106	69541;69542;69543	chr2:178544008;178544007;178544006	chr2:179408735;179408734;179408733
Novex-2	23173	69742;69743;69744	chr2:178544008;178544007;178544006	chr2:179408735;179408734;179408733
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-153
• Domain position: 30
• Structural Position: 46
• Q(SASA): 0.2714
• Predicted PPI site: N

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	None	None	0.892	D	0.796	0.687	0.804337889494	gnomAD-4.0.0	1.59152E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	0
I/V	None	None	0.011	N	0.195	0.087	0.360565625551	gnomAD-4.0.0	1.59151E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85876E-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	0.7881	likely_pathogenic	0.7863	pathogenic	-1.734	Destabilizing	0.845	D	0.723	prob.delet.	None	None	None	None	N
I/C	0.8085	likely_pathogenic	0.8218	pathogenic	-0.956	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
I/D	0.9924	likely_pathogenic	0.9915	pathogenic	-1.145	Destabilizing	0.996	D	0.866	deleterious	None	None	None	None	N
I/E	0.9775	likely_pathogenic	0.9759	pathogenic	-1.078	Destabilizing	0.987	D	0.866	deleterious	None	None	None	None	N
I/F	0.4229	ambiguous	0.4359	ambiguous	-1.081	Destabilizing	0.975	D	0.733	prob.delet.	None	None	None	None	N
I/G	0.964	likely_pathogenic	0.9646	pathogenic	-2.127	Highly Destabilizing	0.987	D	0.859	deleterious	None	None	None	None	N
I/H	0.9514	likely_pathogenic	0.9524	pathogenic	-1.383	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
I/K	0.9246	likely_pathogenic	0.9227	pathogenic	-1.164	Destabilizing	0.983	D	0.867	deleterious	D	0.561274398	None	None	N
I/L	0.1776	likely_benign	0.1777	benign	-0.697	Destabilizing	0.426	N	0.479	neutral	N	0.497500978	None	None	N
I/M	0.1878	likely_benign	0.1916	benign	-0.526	Destabilizing	0.983	D	0.698	prob.neutral	D	0.531306859	None	None	N
I/N	0.8858	likely_pathogenic	0.8775	pathogenic	-1.07	Destabilizing	0.996	D	0.862	deleterious	None	None	None	None	N
I/P	0.9512	likely_pathogenic	0.9509	pathogenic	-1.012	Destabilizing	0.996	D	0.866	deleterious	None	None	None	None	N
I/Q	0.9318	likely_pathogenic	0.9316	pathogenic	-1.142	Destabilizing	0.996	D	0.873	deleterious	None	None	None	None	N
I/R	0.9021	likely_pathogenic	0.9015	pathogenic	-0.691	Destabilizing	0.983	D	0.867	deleterious	D	0.561274398	None	None	N
I/S	0.8511	likely_pathogenic	0.8491	pathogenic	-1.737	Destabilizing	0.975	D	0.845	deleterious	None	None	None	None	N
I/T	0.6779	likely_pathogenic	0.6823	pathogenic	-1.542	Destabilizing	0.892	D	0.796	deleterious	D	0.526533919	None	None	N
I/V	0.0877	likely_benign	0.0895	benign	-1.012	Destabilizing	0.011	N	0.195	neutral	N	0.418898958	None	None	N
I/W	0.9608	likely_pathogenic	0.9633	pathogenic	-1.249	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
I/Y	0.8835	likely_pathogenic	0.885	pathogenic	-0.986	Destabilizing	0.987	D	0.767	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.