TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24679	74260;74261;74262	chr2:178572097;178572096;178572095	chr2:179436824;179436823;179436822
N2AB	23038	69337;69338;69339	chr2:178572097;178572096;178572095	chr2:179436824;179436823;179436822
N2A	22111	66556;66557;66558	chr2:178572097;178572096;178572095	chr2:179436824;179436823;179436822
N2B	15614	47065;47066;47067	chr2:178572097;178572096;178572095	chr2:179436824;179436823;179436822
Novex-1	15739	47440;47441;47442	chr2:178572097;178572096;178572095	chr2:179436824;179436823;179436822
Novex-2	15806	47641;47642;47643	chr2:178572097;178572096;178572095	chr2:179436824;179436823;179436822
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-67
• Domain position: 64
• Structural Position: 97
• Q(SASA): 0.1155
• 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/I	rs752890306	-1.317	0.991	D	0.828	0.629	0.844246078639	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
L/I	rs752890306	-1.317	0.991	D	0.828	0.629	0.844246078639	gnomAD-4.0.0	3.18495E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72001E-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	0.9746	likely_pathogenic	0.9767	pathogenic	-2.383	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/C	0.9241	likely_pathogenic	0.9259	pathogenic	-1.996	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9996	pathogenic	-1.648	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/E	0.998	likely_pathogenic	0.9983	pathogenic	-1.533	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/F	0.9348	likely_pathogenic	0.9166	pathogenic	-1.698	Destabilizing	1.0	D	0.874	deleterious	D	0.653368009	None	None	N
L/G	0.9921	likely_pathogenic	0.9931	pathogenic	-2.829	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/H	0.9949	likely_pathogenic	0.9954	pathogenic	-1.949	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/I	0.5688	likely_pathogenic	0.5458	ambiguous	-1.156	Destabilizing	0.991	D	0.828	deleterious	D	0.617302125	None	None	N
L/K	0.9947	likely_pathogenic	0.9952	pathogenic	-1.607	Destabilizing	0.998	D	0.847	deleterious	None	None	None	None	N
L/M	0.6044	likely_pathogenic	0.5468	ambiguous	-1.113	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
L/N	0.994	likely_pathogenic	0.9952	pathogenic	-1.661	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/P	0.9977	likely_pathogenic	0.9977	pathogenic	-1.539	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/Q	0.9913	likely_pathogenic	0.9926	pathogenic	-1.706	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/R	0.9895	likely_pathogenic	0.9904	pathogenic	-1.113	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/S	0.9969	likely_pathogenic	0.9971	pathogenic	-2.512	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.670194587	None	None	N
L/T	0.9839	likely_pathogenic	0.9856	pathogenic	-2.247	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/V	0.6008	likely_pathogenic	0.5851	pathogenic	-1.539	Destabilizing	0.993	D	0.837	deleterious	D	0.594428548	None	None	N
L/W	0.9944	likely_pathogenic	0.9926	pathogenic	-1.769	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/Y	0.9943	likely_pathogenic	0.9937	pathogenic	-1.548	Destabilizing	0.999	D	0.837	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.