TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19822	59689;59690;59691	chr2:178592541;178592540;178592539	chr2:179457268;179457267;179457266
N2AB	18181	54766;54767;54768	chr2:178592541;178592540;178592539	chr2:179457268;179457267;179457266
N2A	17254	51985;51986;51987	chr2:178592541;178592540;178592539	chr2:179457268;179457267;179457266
N2B	10757	32494;32495;32496	chr2:178592541;178592540;178592539	chr2:179457268;179457267;179457266
Novex-1	10882	32869;32870;32871	chr2:178592541;178592540;178592539	chr2:179457268;179457267;179457266
Novex-2	10949	33070;33071;33072	chr2:178592541;178592540;178592539	chr2:179457268;179457267;179457266
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: Ig-119
• Domain position: 33
• Structural Position: 50
• Q(SASA): 0.2729
• 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
K/E	None	None	0.999	D	0.603	0.533	0.450248222533	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.926	likely_pathogenic	0.9406	pathogenic	-0.984	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
K/C	0.9014	likely_pathogenic	0.9042	pathogenic	-1.199	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/D	0.9815	likely_pathogenic	0.9852	pathogenic	-0.863	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/E	0.8461	likely_pathogenic	0.8752	pathogenic	-0.687	Destabilizing	0.999	D	0.603	neutral	D	0.531260503	None	None	N
K/F	0.9447	likely_pathogenic	0.947	pathogenic	-0.618	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/G	0.948	likely_pathogenic	0.9638	pathogenic	-1.394	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
K/H	0.675	likely_pathogenic	0.7053	pathogenic	-1.744	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
K/I	0.7734	likely_pathogenic	0.7746	pathogenic	0.115	Stabilizing	1.0	D	0.821	deleterious	N	0.492138704	None	None	N
K/L	0.7782	likely_pathogenic	0.8129	pathogenic	0.115	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
K/M	0.5585	ambiguous	0.5804	pathogenic	-0.053	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
K/N	0.9309	likely_pathogenic	0.9434	pathogenic	-1.048	Destabilizing	1.0	D	0.689	prob.neutral	N	0.504508967	None	None	N
K/P	0.9893	likely_pathogenic	0.9932	pathogenic	-0.224	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/Q	0.5024	ambiguous	0.5316	ambiguous	-1.033	Destabilizing	1.0	D	0.667	neutral	D	0.530500034	None	None	N
K/R	0.1087	likely_benign	0.1093	benign	-0.872	Destabilizing	0.999	D	0.601	neutral	N	0.511373897	None	None	N
K/S	0.957	likely_pathogenic	0.9675	pathogenic	-1.706	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
K/T	0.8275	likely_pathogenic	0.85	pathogenic	-1.301	Destabilizing	1.0	D	0.739	prob.delet.	N	0.494545013	None	None	N
K/V	0.755	likely_pathogenic	0.7525	pathogenic	-0.224	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
K/W	0.9151	likely_pathogenic	0.9237	pathogenic	-0.54	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
K/Y	0.841	likely_pathogenic	0.8504	pathogenic	-0.177	Destabilizing	1.0	D	0.792	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.