TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30408	91447;91448;91449	chr2:178551678;178551677;178551676	chr2:179416405;179416404;179416403
N2AB	28767	86524;86525;86526	chr2:178551678;178551677;178551676	chr2:179416405;179416404;179416403
N2A	27840	83743;83744;83745	chr2:178551678;178551677;178551676	chr2:179416405;179416404;179416403
N2B	21343	64252;64253;64254	chr2:178551678;178551677;178551676	chr2:179416405;179416404;179416403
Novex-1	21468	64627;64628;64629	chr2:178551678;178551677;178551676	chr2:179416405;179416404;179416403
Novex-2	21535	64828;64829;64830	chr2:178551678;178551677;178551676	chr2:179416405;179416404;179416403
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-109
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.0849
• 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
S/G	None	None	0.999	N	0.745	0.279	0.154104182512	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
S/R	None	None	1.0	D	0.859	0.546	0.306053231325	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

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
S/A	0.3813	ambiguous	0.4408	ambiguous	-0.993	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
S/C	0.5766	likely_pathogenic	0.6052	pathogenic	-0.61	Destabilizing	1.0	D	0.848	deleterious	D	0.523940938	None	None	N
S/D	0.9885	likely_pathogenic	0.9896	pathogenic	-0.722	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
S/E	0.9963	likely_pathogenic	0.9966	pathogenic	-0.596	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
S/F	0.9899	likely_pathogenic	0.9915	pathogenic	-0.785	Destabilizing	1.0	D	0.928	deleterious	None	None	None	None	N
S/G	0.1021	likely_benign	0.1178	benign	-1.34	Destabilizing	0.999	D	0.745	deleterious	N	0.421213253	None	None	N
S/H	0.9836	likely_pathogenic	0.983	pathogenic	-1.516	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
S/I	0.9903	likely_pathogenic	0.9929	pathogenic	-0.13	Destabilizing	1.0	D	0.924	deleterious	D	0.534790265	None	None	N
S/K	0.9989	likely_pathogenic	0.999	pathogenic	-0.401	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
S/L	0.9437	likely_pathogenic	0.9513	pathogenic	-0.13	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
S/M	0.9757	likely_pathogenic	0.9792	pathogenic	-0.137	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
S/N	0.951	likely_pathogenic	0.9531	pathogenic	-0.725	Destabilizing	0.999	D	0.737	prob.delet.	D	0.534536775	None	None	N
S/P	0.9884	likely_pathogenic	0.988	pathogenic	-0.385	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
S/Q	0.9923	likely_pathogenic	0.9925	pathogenic	-0.668	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
S/R	0.9975	likely_pathogenic	0.9977	pathogenic	-0.538	Destabilizing	1.0	D	0.859	deleterious	D	0.522166512	None	None	N
S/T	0.6786	likely_pathogenic	0.715	pathogenic	-0.623	Destabilizing	0.999	D	0.73	prob.delet.	N	0.511406091	None	None	N
S/V	0.9815	likely_pathogenic	0.9864	pathogenic	-0.385	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
S/W	0.9949	likely_pathogenic	0.9953	pathogenic	-0.839	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
S/Y	0.9864	likely_pathogenic	0.9875	pathogenic	-0.501	Destabilizing	1.0	D	0.931	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.