TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5490	16693;16694;16695	chr2:178732593;178732592;178732591	chr2:179597320;179597319;179597318
N2AB	5173	15742;15743;15744	chr2:178732593;178732592;178732591	chr2:179597320;179597319;179597318
N2A	4246	12961;12962;12963	chr2:178732593;178732592;178732591	chr2:179597320;179597319;179597318
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-38
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.2897
• 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/P	None	None	0.998	N	0.759	0.71	0.897561542109	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
L/V	None	None	0.835	N	0.431	0.228	0.520161069619	gnomAD-4.0.0	6.84262E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99502E-07	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	0.5889	likely_pathogenic	0.7045	pathogenic	-2.114	Highly Destabilizing	0.97	D	0.495	neutral	None	None	None	None	I
L/C	0.8467	likely_pathogenic	0.9013	pathogenic	-1.213	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	I
L/D	0.9758	likely_pathogenic	0.9868	pathogenic	-2.257	Highly Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	I
L/E	0.8376	likely_pathogenic	0.8866	pathogenic	-2.038	Highly Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	I
L/F	0.2847	likely_benign	0.4065	ambiguous	-1.265	Destabilizing	0.991	D	0.495	neutral	None	None	None	None	I
L/G	0.929	likely_pathogenic	0.954	pathogenic	-2.61	Highly Destabilizing	0.996	D	0.722	prob.delet.	None	None	None	None	I
L/H	0.7694	likely_pathogenic	0.8453	pathogenic	-1.866	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
L/I	0.0853	likely_benign	0.1096	benign	-0.693	Destabilizing	0.304	N	0.193	neutral	None	None	None	None	I
L/K	0.782	likely_pathogenic	0.8259	pathogenic	-1.557	Destabilizing	0.996	D	0.671	neutral	None	None	None	None	I
L/M	0.1452	likely_benign	0.1656	benign	-0.555	Destabilizing	0.835	D	0.418	neutral	D	0.535913422	None	None	I
L/N	0.9166	likely_pathogenic	0.945	pathogenic	-1.919	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
L/P	0.9258	likely_pathogenic	0.9567	pathogenic	-1.147	Destabilizing	0.998	D	0.759	deleterious	N	0.518331165	None	None	I
L/Q	0.641	likely_pathogenic	0.699	pathogenic	-1.797	Destabilizing	0.994	D	0.712	prob.delet.	D	0.523851347	None	None	I
L/R	0.6718	likely_pathogenic	0.7425	pathogenic	-1.293	Destabilizing	0.994	D	0.701	prob.neutral	D	0.525737451	None	None	I
L/S	0.8733	likely_pathogenic	0.9237	pathogenic	-2.574	Highly Destabilizing	0.996	D	0.621	neutral	None	None	None	None	I
L/T	0.6066	likely_pathogenic	0.7178	pathogenic	-2.21	Highly Destabilizing	0.996	D	0.545	neutral	None	None	None	None	I
L/V	0.1167	likely_benign	0.1472	benign	-1.147	Destabilizing	0.835	D	0.431	neutral	N	0.497661678	None	None	I
L/W	0.5519	ambiguous	0.6732	pathogenic	-1.58	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
L/Y	0.6673	likely_pathogenic	0.7728	pathogenic	-1.241	Destabilizing	0.999	D	0.634	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.