TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29682	89269;89270;89271	chr2:178554067;178554066;178554065	chr2:179418794;179418793;179418792
N2AB	28041	84346;84347;84348	chr2:178554067;178554066;178554065	chr2:179418794;179418793;179418792
N2A	27114	81565;81566;81567	chr2:178554067;178554066;178554065	chr2:179418794;179418793;179418792
N2B	20617	62074;62075;62076	chr2:178554067;178554066;178554065	chr2:179418794;179418793;179418792
Novex-1	20742	62449;62450;62451	chr2:178554067;178554066;178554065	chr2:179418794;179418793;179418792
Novex-2	20809	62650;62651;62652	chr2:178554067;178554066;178554065	chr2:179418794;179418793;179418792
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-104
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.5773
• 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
K/Q	rs370563246	-0.279	1.0	N	0.734	0.404	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	3.56E-05	0
K/Q	rs370563246	-0.279	1.0	N	0.734	0.404	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
K/Q	rs370563246	-0.279	1.0	N	0.734	0.404	None	gnomAD-4.0.0	1.85903E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.54277E-05	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
K/A	0.6804	likely_pathogenic	0.7837	pathogenic	-0.498	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
K/C	0.815	likely_pathogenic	0.8617	pathogenic	-0.632	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
K/D	0.925	likely_pathogenic	0.958	pathogenic	0.037	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
K/E	0.6044	likely_pathogenic	0.7421	pathogenic	0.179	Stabilizing	0.999	D	0.655	neutral	N	0.490196122	None	None	I
K/F	0.9311	likely_pathogenic	0.9571	pathogenic	-0.04	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
K/G	0.8117	likely_pathogenic	0.8768	pathogenic	-0.878	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	I
K/H	0.4598	ambiguous	0.5336	ambiguous	-1.039	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
K/I	0.6992	likely_pathogenic	0.788	pathogenic	0.491	Stabilizing	1.0	D	0.75	deleterious	D	0.523444691	None	None	I
K/L	0.6017	likely_pathogenic	0.6931	pathogenic	0.491	Stabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	I
K/M	0.5471	ambiguous	0.6564	pathogenic	0.118	Stabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
K/N	0.8395	likely_pathogenic	0.9022	pathogenic	-0.518	Destabilizing	1.0	D	0.766	deleterious	N	0.476813288	None	None	I
K/P	0.6197	likely_pathogenic	0.7087	pathogenic	0.192	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
K/Q	0.2594	likely_benign	0.3411	ambiguous	-0.479	Destabilizing	1.0	D	0.734	prob.delet.	N	0.511515544	None	None	I
K/R	0.0699	likely_benign	0.0737	benign	-0.53	Destabilizing	0.999	D	0.588	neutral	N	0.426667506	None	None	I
K/S	0.7903	likely_pathogenic	0.869	pathogenic	-1.15	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
K/T	0.4975	ambiguous	0.6094	pathogenic	-0.795	Destabilizing	1.0	D	0.76	deleterious	N	0.486638529	None	None	I
K/V	0.6263	likely_pathogenic	0.7195	pathogenic	0.192	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
K/W	0.8759	likely_pathogenic	0.9176	pathogenic	0.049	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
K/Y	0.8437	likely_pathogenic	0.8933	pathogenic	0.331	Stabilizing	1.0	D	0.731	prob.delet.	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.