TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30501	91726;91727;91728	chr2:178551030;178551029;178551028	chr2:179415757;179415756;179415755
N2AB	28860	86803;86804;86805	chr2:178551030;178551029;178551028	chr2:179415757;179415756;179415755
N2A	27933	84022;84023;84024	chr2:178551030;178551029;178551028	chr2:179415757;179415756;179415755
N2B	21436	64531;64532;64533	chr2:178551030;178551029;178551028	chr2:179415757;179415756;179415755
Novex-1	21561	64906;64907;64908	chr2:178551030;178551029;178551028	chr2:179415757;179415756;179415755
Novex-2	21628	65107;65108;65109	chr2:178551030;178551029;178551028	chr2:179415757;179415756;179415755
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-110
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.4976
• Predicted PPI site: I

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/V	rs1299510786	-0.064	1.0	D	0.627	0.392	0.57733738444	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
A/V	rs1299510786	-0.064	1.0	D	0.627	0.392	0.57733738444	gnomAD-4.0.0	3.18468E-06	None	None	None	None	I	None	0	0	None	0	2.77948E-05	None	0	0	2.85974E-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
A/C	0.8313	likely_pathogenic	0.7893	pathogenic	-0.809	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
A/D	0.9503	likely_pathogenic	0.9262	pathogenic	-0.312	Destabilizing	1.0	D	0.754	deleterious	N	0.466167256	None	None	I
A/E	0.8925	likely_pathogenic	0.8569	pathogenic	-0.453	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
A/F	0.8339	likely_pathogenic	0.7921	pathogenic	-0.974	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
A/G	0.4341	ambiguous	0.3651	ambiguous	-0.504	Destabilizing	1.0	D	0.525	neutral	N	0.463056537	None	None	I
A/H	0.9223	likely_pathogenic	0.8959	pathogenic	-0.516	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
A/I	0.6502	likely_pathogenic	0.5585	ambiguous	-0.404	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
A/K	0.9645	likely_pathogenic	0.9425	pathogenic	-0.599	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
A/L	0.5689	likely_pathogenic	0.477	ambiguous	-0.404	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
A/M	0.5647	likely_pathogenic	0.5014	ambiguous	-0.338	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
A/N	0.7985	likely_pathogenic	0.7245	pathogenic	-0.302	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
A/P	0.966	likely_pathogenic	0.9356	pathogenic	-0.375	Destabilizing	1.0	D	0.733	prob.delet.	D	0.523850123	None	None	I
A/Q	0.8331	likely_pathogenic	0.7809	pathogenic	-0.583	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
A/R	0.9118	likely_pathogenic	0.8764	pathogenic	-0.171	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
A/S	0.1944	likely_benign	0.1733	benign	-0.59	Destabilizing	1.0	D	0.543	neutral	N	0.489601477	None	None	I
A/T	0.3198	likely_benign	0.2397	benign	-0.646	Destabilizing	1.0	D	0.706	prob.neutral	N	0.511438186	None	None	I
A/V	0.4118	ambiguous	0.3211	benign	-0.375	Destabilizing	1.0	D	0.627	neutral	D	0.522983331	None	None	I
A/W	0.9759	likely_pathogenic	0.9671	pathogenic	-1.099	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
A/Y	0.9144	likely_pathogenic	0.8868	pathogenic	-0.741	Destabilizing	1.0	D	0.733	prob.delet.	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.