TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25250	75973;75974;75975	chr2:178570384;178570383;178570382	chr2:179435111;179435110;179435109
N2AB	23609	71050;71051;71052	chr2:178570384;178570383;178570382	chr2:179435111;179435110;179435109
N2A	22682	68269;68270;68271	chr2:178570384;178570383;178570382	chr2:179435111;179435110;179435109
N2B	16185	48778;48779;48780	chr2:178570384;178570383;178570382	chr2:179435111;179435110;179435109
Novex-1	16310	49153;49154;49155	chr2:178570384;178570383;178570382	chr2:179435111;179435110;179435109
Novex-2	16377	49354;49355;49356	chr2:178570384;178570383;178570382	chr2:179435111;179435110;179435109
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: Fn3-71
• Domain position: 47
• Structural Position: 63
• Q(SASA): 1.0262
• 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/F	rs1231715116	-0.54	0.988	N	0.652	0.298	0.437958778045	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/F	rs1231715116	-0.54	0.988	N	0.652	0.298	0.437958778045	gnomAD-4.0.0	1.59251E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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	0.7438	likely_pathogenic	0.7422	pathogenic	-0.472	Destabilizing	0.968	D	0.6	neutral	None	None	None	None	I
L/C	0.9235	likely_pathogenic	0.9281	pathogenic	-0.81	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
L/D	0.9712	likely_pathogenic	0.9736	pathogenic	-0.183	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	I
L/E	0.9021	likely_pathogenic	0.9064	pathogenic	-0.264	Destabilizing	0.995	D	0.711	prob.delet.	None	None	None	None	I
L/F	0.6754	likely_pathogenic	0.6543	pathogenic	-0.573	Destabilizing	0.988	D	0.652	neutral	N	0.485941094	None	None	I
L/G	0.9116	likely_pathogenic	0.9145	pathogenic	-0.58	Destabilizing	0.995	D	0.703	prob.neutral	None	None	None	None	I
L/H	0.8283	likely_pathogenic	0.8354	pathogenic	0.124	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
L/I	0.2252	likely_benign	0.2125	benign	-0.3	Destabilizing	0.919	D	0.507	neutral	N	0.499394396	None	None	I
L/K	0.7797	likely_pathogenic	0.7924	pathogenic	-0.346	Destabilizing	0.991	D	0.654	neutral	None	None	None	None	I
L/M	0.2828	likely_benign	0.2802	benign	-0.638	Destabilizing	0.862	D	0.513	neutral	None	None	None	None	I
L/N	0.8698	likely_pathogenic	0.8819	pathogenic	-0.245	Destabilizing	0.995	D	0.727	prob.delet.	None	None	None	None	I
L/P	0.7792	likely_pathogenic	0.795	pathogenic	-0.33	Destabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	I
L/Q	0.7218	likely_pathogenic	0.7414	pathogenic	-0.401	Destabilizing	0.995	D	0.687	prob.neutral	None	None	None	None	I
L/R	0.6997	likely_pathogenic	0.7068	pathogenic	0.105	Stabilizing	0.995	D	0.679	prob.neutral	None	None	None	None	I
L/S	0.8899	likely_pathogenic	0.8936	pathogenic	-0.641	Destabilizing	0.988	D	0.655	neutral	N	0.473399873	None	None	I
L/T	0.7613	likely_pathogenic	0.7721	pathogenic	-0.62	Destabilizing	0.991	D	0.635	neutral	None	None	None	None	I
L/V	0.2912	likely_benign	0.2759	benign	-0.33	Destabilizing	0.919	D	0.549	neutral	N	0.470322282	None	None	I
L/W	0.7822	likely_pathogenic	0.7637	pathogenic	-0.592	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
L/Y	0.8572	likely_pathogenic	0.8559	pathogenic	-0.365	Destabilizing	0.995	D	0.681	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.