TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30166	90721;90722;90723	chr2:178552404;178552403;178552402	chr2:179417131;179417130;179417129
N2AB	28525	85798;85799;85800	chr2:178552404;178552403;178552402	chr2:179417131;179417130;179417129
N2A	27598	83017;83018;83019	chr2:178552404;178552403;178552402	chr2:179417131;179417130;179417129
N2B	21101	63526;63527;63528	chr2:178552404;178552403;178552402	chr2:179417131;179417130;179417129
Novex-1	21226	63901;63902;63903	chr2:178552404;178552403;178552402	chr2:179417131;179417130;179417129
Novex-2	21293	64102;64103;64104	chr2:178552404;178552403;178552402	chr2:179417131;179417130;179417129
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-148
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1981
• 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
L/P	None	None	0.983	N	0.764	0.345	0.700973683922	gnomAD-4.0.0	1.64581E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.96265E-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
L/A	0.5026	ambiguous	0.3844	ambiguous	-1.997	Destabilizing	0.633	D	0.577	neutral	None	None	None	None	N
L/C	0.5409	ambiguous	0.4889	ambiguous	-1.308	Destabilizing	0.996	D	0.687	prob.neutral	None	None	None	None	N
L/D	0.8834	likely_pathogenic	0.7997	pathogenic	-1.468	Destabilizing	0.961	D	0.761	deleterious	None	None	None	None	N
L/E	0.4617	ambiguous	0.3455	ambiguous	-1.355	Destabilizing	0.961	D	0.741	deleterious	None	None	None	None	N
L/F	0.1773	likely_benign	0.1382	benign	-1.243	Destabilizing	0.923	D	0.586	neutral	None	None	None	None	N
L/G	0.7609	likely_pathogenic	0.6606	pathogenic	-2.431	Highly Destabilizing	0.961	D	0.74	deleterious	None	None	None	None	N
L/H	0.2993	likely_benign	0.2294	benign	-1.729	Destabilizing	0.996	D	0.749	deleterious	None	None	None	None	N
L/I	0.1352	likely_benign	0.1108	benign	-0.815	Destabilizing	0.372	N	0.501	neutral	None	None	None	None	N
L/K	0.3432	ambiguous	0.2534	benign	-1.294	Destabilizing	0.923	D	0.705	prob.neutral	None	None	None	None	N
L/M	0.1061	likely_benign	0.0954	benign	-0.726	Destabilizing	0.19	N	0.328	neutral	N	0.51127511	None	None	N
L/N	0.5419	ambiguous	0.4224	ambiguous	-1.31	Destabilizing	0.961	D	0.764	deleterious	None	None	None	None	N
L/P	0.9859	likely_pathogenic	0.978	pathogenic	-1.182	Destabilizing	0.983	D	0.764	deleterious	N	0.516008926	None	None	N
L/Q	0.157	likely_benign	0.1212	benign	-1.335	Destabilizing	0.949	D	0.737	prob.delet.	N	0.511448468	None	None	N
L/R	0.3208	likely_benign	0.2476	benign	-0.904	Destabilizing	0.949	D	0.739	prob.delet.	N	0.501404833	None	None	N
L/S	0.4847	ambiguous	0.3444	ambiguous	-2.063	Highly Destabilizing	0.858	D	0.695	prob.neutral	None	None	None	None	N
L/T	0.3213	likely_benign	0.2469	benign	-1.819	Destabilizing	0.096	N	0.363	neutral	None	None	None	None	N
L/V	0.1421	likely_benign	0.1176	benign	-1.182	Destabilizing	0.008	N	0.385	neutral	N	0.456959562	None	None	N
L/W	0.3421	ambiguous	0.306	benign	-1.446	Destabilizing	0.996	D	0.736	prob.delet.	None	None	None	None	N
L/Y	0.3723	ambiguous	0.2984	benign	-1.167	Destabilizing	0.961	D	0.713	prob.delet.	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.