TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18512	55759;55760;55761	chr2:178601463;178601462;178601461	chr2:179466190;179466189;179466188
N2AB	16871	50836;50837;50838	chr2:178601463;178601462;178601461	chr2:179466190;179466189;179466188
N2A	15944	48055;48056;48057	chr2:178601463;178601462;178601461	chr2:179466190;179466189;179466188
N2B	9447	28564;28565;28566	chr2:178601463;178601462;178601461	chr2:179466190;179466189;179466188
Novex-1	9572	28939;28940;28941	chr2:178601463;178601462;178601461	chr2:179466190;179466189;179466188
Novex-2	9639	29140;29141;29142	chr2:178601463;178601462;178601461	chr2:179466190;179466189;179466188
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: Fn3-22
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.4249
• 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/E	None	None	0.939	N	0.522	0.255	0.296679040009	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.4784	ambiguous	0.5832	pathogenic	-0.102	Destabilizing	0.953	D	0.587	neutral	None	None	None	None	I
K/C	0.6843	likely_pathogenic	0.7515	pathogenic	-0.102	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	I
K/D	0.834	likely_pathogenic	0.8786	pathogenic	0.002	Stabilizing	0.993	D	0.754	deleterious	None	None	None	None	I
K/E	0.4241	ambiguous	0.4868	ambiguous	0.022	Stabilizing	0.939	D	0.522	neutral	N	0.485502379	None	None	I
K/F	0.8444	likely_pathogenic	0.8916	pathogenic	-0.195	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	I
K/G	0.647	likely_pathogenic	0.741	pathogenic	-0.354	Destabilizing	0.993	D	0.661	neutral	None	None	None	None	I
K/H	0.3249	likely_benign	0.3711	ambiguous	-0.737	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	I
K/I	0.4669	ambiguous	0.5366	ambiguous	0.495	Stabilizing	0.991	D	0.806	deleterious	N	0.443002395	None	None	I
K/L	0.4565	ambiguous	0.5272	ambiguous	0.495	Stabilizing	0.986	D	0.661	neutral	None	None	None	None	I
K/M	0.3674	ambiguous	0.4356	ambiguous	0.451	Stabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
K/N	0.6402	likely_pathogenic	0.6992	pathogenic	0.237	Stabilizing	0.982	D	0.667	neutral	N	0.487715965	None	None	I
K/P	0.941	likely_pathogenic	0.9589	pathogenic	0.326	Stabilizing	0.998	D	0.757	deleterious	None	None	None	None	I
K/Q	0.193	likely_benign	0.2268	benign	0.006	Stabilizing	0.982	D	0.669	neutral	N	0.469687564	None	None	I
K/R	0.0793	likely_benign	0.0843	benign	-0.091	Destabilizing	0.046	N	0.157	neutral	N	0.4798272	None	None	I
K/S	0.5591	ambiguous	0.6404	pathogenic	-0.308	Destabilizing	0.953	D	0.611	neutral	None	None	None	None	I
K/T	0.2213	likely_benign	0.2582	benign	-0.127	Destabilizing	0.991	D	0.689	prob.neutral	N	0.402094348	None	None	I
K/V	0.4308	ambiguous	0.4992	ambiguous	0.326	Stabilizing	0.993	D	0.782	deleterious	None	None	None	None	I
K/W	0.7719	likely_pathogenic	0.8399	pathogenic	-0.132	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	I
K/Y	0.7358	likely_pathogenic	0.7991	pathogenic	0.202	Stabilizing	0.998	D	0.779	deleterious	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.