TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30415	91468;91469;91470	chr2:178551657;178551656;178551655	chr2:179416384;179416383;179416382
N2AB	28774	86545;86546;86547	chr2:178551657;178551656;178551655	chr2:179416384;179416383;179416382
N2A	27847	83764;83765;83766	chr2:178551657;178551656;178551655	chr2:179416384;179416383;179416382
N2B	21350	64273;64274;64275	chr2:178551657;178551656;178551655	chr2:179416384;179416383;179416382
Novex-1	21475	64648;64649;64650	chr2:178551657;178551656;178551655	chr2:179416384;179416383;179416382
Novex-2	21542	64849;64850;64851	chr2:178551657;178551656;178551655	chr2:179416384;179416383;179416382
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: Fn3-109
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.9324
• 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/N	None	None	0.999	N	0.831	0.166	0.154104182512	gnomAD-4.0.0	1.39005E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.81873E-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	0.4475	ambiguous	0.4606	ambiguous	-0.094	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	I
K/C	0.7581	likely_pathogenic	0.7475	pathogenic	-0.282	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
K/D	0.6515	likely_pathogenic	0.6578	pathogenic	0.33	Stabilizing	0.999	D	0.855	deleterious	None	None	None	None	I
K/E	0.3414	ambiguous	0.3625	ambiguous	0.375	Stabilizing	0.997	D	0.719	prob.delet.	N	0.388298332	None	None	I
K/F	0.8765	likely_pathogenic	0.8821	pathogenic	-0.091	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
K/G	0.5389	ambiguous	0.5565	ambiguous	-0.354	Destabilizing	0.999	D	0.737	deleterious	None	None	None	None	I
K/H	0.4053	ambiguous	0.4105	ambiguous	-0.593	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
K/I	0.515	ambiguous	0.5184	ambiguous	0.526	Stabilizing	0.999	D	0.807	deleterious	N	0.506989585	None	None	I
K/L	0.5058	ambiguous	0.5137	ambiguous	0.526	Stabilizing	0.999	D	0.737	deleterious	None	None	None	None	I
K/M	0.4564	ambiguous	0.4605	ambiguous	0.242	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
K/N	0.5639	ambiguous	0.5752	pathogenic	0.139	Stabilizing	0.999	D	0.831	deleterious	N	0.462718733	None	None	I
K/P	0.5292	ambiguous	0.5261	ambiguous	0.349	Stabilizing	0.999	D	0.857	deleterious	None	None	None	None	I
K/Q	0.2091	likely_benign	0.2154	benign	0.019	Stabilizing	0.999	D	0.811	deleterious	N	0.462430731	None	None	I
K/R	0.0831	likely_benign	0.0841	benign	-0.117	Destabilizing	0.997	D	0.657	prob.neutral	N	0.466393756	None	None	I
K/S	0.5257	ambiguous	0.5349	ambiguous	-0.447	Destabilizing	0.998	D	0.725	deleterious	None	None	None	None	I
K/T	0.3131	likely_benign	0.3216	benign	-0.229	Destabilizing	0.999	D	0.851	deleterious	N	0.482168498	None	None	I
K/V	0.4464	ambiguous	0.4518	ambiguous	0.349	Stabilizing	0.999	D	0.819	deleterious	None	None	None	None	I
K/W	0.8508	likely_pathogenic	0.8531	pathogenic	-0.048	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
K/Y	0.7234	likely_pathogenic	0.7292	pathogenic	0.279	Stabilizing	1.0	D	0.826	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.