TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25966	78121;78122;78123	chr2:178568236;178568235;178568234	chr2:179432963;179432962;179432961
N2AB	24325	73198;73199;73200	chr2:178568236;178568235;178568234	chr2:179432963;179432962;179432961
N2A	23398	70417;70418;70419	chr2:178568236;178568235;178568234	chr2:179432963;179432962;179432961
N2B	16901	50926;50927;50928	chr2:178568236;178568235;178568234	chr2:179432963;179432962;179432961
Novex-1	17026	51301;51302;51303	chr2:178568236;178568235;178568234	chr2:179432963;179432962;179432961
Novex-2	17093	51502;51503;51504	chr2:178568236;178568235;178568234	chr2:179432963;179432962;179432961
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-76
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1064
• 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
F/L	None	None	0.698	N	0.726	0.189	0.350524144436	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
F/A	0.3823	ambiguous	0.38	ambiguous	-3.447	Highly Destabilizing	0.86	D	0.694	prob.neutral	None	None	None	None	N
F/C	0.1959	likely_benign	0.1802	benign	-1.971	Destabilizing	0.997	D	0.752	deleterious	N	0.503800138	None	None	N
F/D	0.8857	likely_pathogenic	0.8839	pathogenic	-3.37	Highly Destabilizing	0.956	D	0.782	deleterious	None	None	None	None	N
F/E	0.8638	likely_pathogenic	0.8534	pathogenic	-3.237	Highly Destabilizing	0.956	D	0.751	deleterious	None	None	None	None	N
F/G	0.7603	likely_pathogenic	0.7678	pathogenic	-3.805	Highly Destabilizing	0.956	D	0.747	deleterious	None	None	None	None	N
F/H	0.4445	ambiguous	0.4063	ambiguous	-1.981	Destabilizing	0.043	N	0.569	neutral	None	None	None	None	N
F/I	0.1862	likely_benign	0.153	benign	-2.278	Highly Destabilizing	0.942	D	0.733	prob.delet.	N	0.467647337	None	None	N
F/K	0.776	likely_pathogenic	0.7502	pathogenic	-2.234	Highly Destabilizing	0.956	D	0.771	deleterious	None	None	None	None	N
F/L	0.6768	likely_pathogenic	0.6452	pathogenic	-2.278	Highly Destabilizing	0.698	D	0.726	prob.delet.	N	0.496026017	None	None	N
F/M	0.3683	ambiguous	0.356	ambiguous	-1.836	Destabilizing	0.998	D	0.738	prob.delet.	None	None	None	None	N
F/N	0.614	likely_pathogenic	0.5939	pathogenic	-2.439	Highly Destabilizing	0.956	D	0.782	deleterious	None	None	None	None	N
F/P	0.998	likely_pathogenic	0.9977	pathogenic	-2.677	Highly Destabilizing	0.993	D	0.808	deleterious	None	None	None	None	N
F/Q	0.6673	likely_pathogenic	0.6406	pathogenic	-2.589	Highly Destabilizing	0.956	D	0.801	deleterious	None	None	None	None	N
F/R	0.6301	likely_pathogenic	0.5872	pathogenic	-1.365	Destabilizing	0.956	D	0.789	deleterious	None	None	None	None	N
F/S	0.2473	likely_benign	0.2709	benign	-3.106	Highly Destabilizing	0.942	D	0.731	prob.delet.	N	0.418085308	None	None	N
F/T	0.3274	likely_benign	0.3472	ambiguous	-2.888	Highly Destabilizing	0.978	D	0.729	prob.delet.	None	None	None	None	N
F/V	0.1758	likely_benign	0.1566	benign	-2.677	Highly Destabilizing	0.822	D	0.721	prob.delet.	N	0.455006113	None	None	N
F/W	0.5177	ambiguous	0.4879	ambiguous	-0.98	Destabilizing	0.994	D	0.741	deleterious	None	None	None	None	N
F/Y	0.1528	likely_benign	0.132	benign	-1.393	Destabilizing	0.006	N	0.312	neutral	N	0.484000869	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.