TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5974	18145;18146;18147	chr2:178730613;178730612;178730611	chr2:179595340;179595339;179595338
N2AB	5657	17194;17195;17196	chr2:178730613;178730612;178730611	chr2:179595340;179595339;179595338
N2A	4730	14413;14414;14415	chr2:178730613;178730612;178730611	chr2:179595340;179595339;179595338
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-43
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.096
• 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
A/S	rs761789723	-1.556	1.0	N	0.599	0.301	0.228597637076	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	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	0.769	likely_pathogenic	0.7349	pathogenic	-0.629	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
A/D	0.9953	likely_pathogenic	0.9951	pathogenic	-2.276	Highly Destabilizing	1.0	D	0.84	deleterious	N	0.478026331	None	None	N
A/E	0.9921	likely_pathogenic	0.9922	pathogenic	-2.012	Highly Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
A/F	0.9497	likely_pathogenic	0.9403	pathogenic	-0.475	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
A/G	0.5115	ambiguous	0.466	ambiguous	-1.509	Destabilizing	1.0	D	0.595	neutral	N	0.472255362	None	None	N
A/H	0.9898	likely_pathogenic	0.9889	pathogenic	-2.061	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
A/I	0.7967	likely_pathogenic	0.7654	pathogenic	0.375	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
A/K	0.9973	likely_pathogenic	0.9974	pathogenic	-0.749	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
A/L	0.7565	likely_pathogenic	0.7257	pathogenic	0.375	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
A/M	0.8534	likely_pathogenic	0.8239	pathogenic	0.053	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/N	0.9812	likely_pathogenic	0.9779	pathogenic	-1.249	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
A/P	0.9843	likely_pathogenic	0.9849	pathogenic	-0.053	Destabilizing	1.0	D	0.823	deleterious	N	0.472999902	None	None	N
A/Q	0.9834	likely_pathogenic	0.9834	pathogenic	-0.904	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/R	0.9877	likely_pathogenic	0.9881	pathogenic	-1.125	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/S	0.3938	ambiguous	0.3641	ambiguous	-1.561	Destabilizing	1.0	D	0.599	neutral	N	0.462537013	None	None	N
A/T	0.5625	ambiguous	0.5096	ambiguous	-1.177	Destabilizing	1.0	D	0.717	prob.delet.	N	0.496265585	None	None	N
A/V	0.509	ambiguous	0.4658	ambiguous	-0.053	Destabilizing	1.0	D	0.633	neutral	N	0.483067001	None	None	N
A/W	0.9963	likely_pathogenic	0.9959	pathogenic	-1.337	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
A/Y	0.9782	likely_pathogenic	0.9759	pathogenic	-0.805	Destabilizing	1.0	D	0.849	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.