TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34946	105061;105062;105063	chr2:178531779;178531778;178531777	chr2:179396506;179396505;179396504
N2AB	33305	100138;100139;100140	chr2:178531779;178531778;178531777	chr2:179396506;179396505;179396504
N2A	32378	97357;97358;97359	chr2:178531779;178531778;178531777	chr2:179396506;179396505;179396504
N2B	25881	77866;77867;77868	chr2:178531779;178531778;178531777	chr2:179396506;179396505;179396504
Novex-1	26006	78241;78242;78243	chr2:178531779;178531778;178531777	chr2:179396506;179396505;179396504
Novex-2	26073	78442;78443;78444	chr2:178531779;178531778;178531777	chr2:179396506;179396505;179396504
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-163
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.4136
• 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
L/R	rs1185207035	None	0.999	N	0.707	0.535	0.774190524746	gnomAD-4.0.0	2.05242E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99402E-07	0	3.31268E-05

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	0.8831	likely_pathogenic	0.9239	pathogenic	-0.996	Destabilizing	0.983	D	0.439	neutral	None	None	None	None	I
L/C	0.951	likely_pathogenic	0.9658	pathogenic	-0.753	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
L/D	0.9954	likely_pathogenic	0.9979	pathogenic	-0.313	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	I
L/E	0.9588	likely_pathogenic	0.981	pathogenic	-0.363	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
L/F	0.7462	likely_pathogenic	0.8424	pathogenic	-0.706	Destabilizing	0.998	D	0.611	neutral	None	None	None	None	I
L/G	0.9716	likely_pathogenic	0.9815	pathogenic	-1.234	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	I
L/H	0.9411	likely_pathogenic	0.9713	pathogenic	-0.369	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
L/I	0.3326	likely_benign	0.4107	ambiguous	-0.462	Destabilizing	0.923	D	0.397	neutral	None	None	None	None	I
L/K	0.9193	likely_pathogenic	0.9576	pathogenic	-0.629	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	I
L/M	0.3662	ambiguous	0.4342	ambiguous	-0.437	Destabilizing	0.997	D	0.618	neutral	N	0.431009825	None	None	I
L/N	0.9653	likely_pathogenic	0.9807	pathogenic	-0.465	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	I
L/P	0.9897	likely_pathogenic	0.9945	pathogenic	-0.606	Destabilizing	0.999	D	0.73	prob.delet.	N	0.463159529	None	None	I
L/Q	0.8226	likely_pathogenic	0.9055	pathogenic	-0.663	Destabilizing	0.999	D	0.703	prob.neutral	N	0.388330909	None	None	I
L/R	0.8568	likely_pathogenic	0.9305	pathogenic	-0.029	Destabilizing	0.999	D	0.707	prob.neutral	N	0.424427782	None	None	I
L/S	0.9457	likely_pathogenic	0.9712	pathogenic	-1.021	Destabilizing	0.998	D	0.666	neutral	None	None	None	None	I
L/T	0.8645	likely_pathogenic	0.9146	pathogenic	-0.957	Destabilizing	0.983	D	0.549	neutral	None	None	None	None	I
L/V	0.2834	likely_benign	0.3895	ambiguous	-0.606	Destabilizing	0.198	N	0.181	neutral	N	0.376809981	None	None	I
L/W	0.9236	likely_pathogenic	0.9648	pathogenic	-0.72	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
L/Y	0.9476	likely_pathogenic	0.9688	pathogenic	-0.496	Destabilizing	0.999	D	0.679	prob.neutral	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.