TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16238	48937;48938;48939	chr2:178614895;178614894;178614893	chr2:179479622;179479621;179479620
N2AB	14597	44014;44015;44016	chr2:178614895;178614894;178614893	chr2:179479622;179479621;179479620
N2A	13670	41233;41234;41235	chr2:178614895;178614894;178614893	chr2:179479622;179479621;179479620
N2B	7173	21742;21743;21744	chr2:178614895;178614894;178614893	chr2:179479622;179479621;179479620
Novex-1	7298	22117;22118;22119	chr2:178614895;178614894;178614893	chr2:179479622;179479621;179479620
Novex-2	7365	22318;22319;22320	chr2:178614895;178614894;178614893	chr2:179479622;179479621;179479620
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: Fn3-5
• Domain position: 84
• Structural Position: 118
• Q(SASA): 0.0744
• 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	rs2057023163	None	0.104	N	0.437	0.086	0.152612264143	gnomAD-4.0.0	2.09737E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.7403E-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	0.5254	ambiguous	0.5131	ambiguous	-0.711	Destabilizing	0.98	D	0.683	prob.neutral	None	None	None	None	N
S/C	0.8177	likely_pathogenic	0.7946	pathogenic	-0.728	Destabilizing	1.0	D	0.741	deleterious	D	0.774073833	None	None	N
S/D	0.9932	likely_pathogenic	0.99	pathogenic	-1.355	Destabilizing	0.996	D	0.748	deleterious	None	None	None	None	N
S/E	0.9973	likely_pathogenic	0.9961	pathogenic	-1.269	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
S/F	0.9979	likely_pathogenic	0.9967	pathogenic	-0.499	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
S/G	0.1236	likely_benign	0.1224	benign	-1.038	Destabilizing	0.104	N	0.437	neutral	N	0.44840041	None	None	N
S/H	0.9949	likely_pathogenic	0.993	pathogenic	-1.46	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
S/I	0.9977	likely_pathogenic	0.9969	pathogenic	0.08	Stabilizing	0.999	D	0.857	deleterious	D	0.719587969	None	None	N
S/K	0.9992	likely_pathogenic	0.999	pathogenic	-1.0	Destabilizing	0.996	D	0.76	deleterious	None	None	None	None	N
S/L	0.986	likely_pathogenic	0.9805	pathogenic	0.08	Stabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
S/M	0.9923	likely_pathogenic	0.9903	pathogenic	0.146	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
S/N	0.977	likely_pathogenic	0.9704	pathogenic	-1.275	Destabilizing	0.994	D	0.749	deleterious	D	0.771962851	None	None	N
S/P	0.9959	likely_pathogenic	0.9934	pathogenic	-0.148	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
S/Q	0.9948	likely_pathogenic	0.9938	pathogenic	-1.259	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
S/R	0.9981	likely_pathogenic	0.9976	pathogenic	-1.01	Destabilizing	0.999	D	0.787	deleterious	D	0.73965802	None	None	N
S/T	0.8669	likely_pathogenic	0.8363	pathogenic	-1.057	Destabilizing	0.994	D	0.72	prob.delet.	D	0.700734568	None	None	N
S/V	0.9937	likely_pathogenic	0.9922	pathogenic	-0.148	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
S/W	0.9979	likely_pathogenic	0.9962	pathogenic	-0.656	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
S/Y	0.9963	likely_pathogenic	0.9942	pathogenic	-0.335	Destabilizing	1.0	D	0.852	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.