TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21280	64063;64064;64065	chr2:178587373;178587372;178587371	chr2:179452100;179452099;179452098
N2AB	19639	59140;59141;59142	chr2:178587373;178587372;178587371	chr2:179452100;179452099;179452098
N2A	18712	56359;56360;56361	chr2:178587373;178587372;178587371	chr2:179452100;179452099;179452098
N2B	12215	36868;36869;36870	chr2:178587373;178587372;178587371	chr2:179452100;179452099;179452098
Novex-1	12340	37243;37244;37245	chr2:178587373;178587372;178587371	chr2:179452100;179452099;179452098
Novex-2	12407	37444;37445;37446	chr2:178587373;178587372;178587371	chr2:179452100;179452099;179452098
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: Fn3-42
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.478
• 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/Q	None	None	0.999	N	0.669	0.192	0.18274738541	gnomAD-4.0.0	1.59585E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86467E-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	0.5001	ambiguous	0.4809	ambiguous	-0.306	Destabilizing	0.997	D	0.535	neutral	None	None	None	None	N
K/C	0.8135	likely_pathogenic	0.8351	pathogenic	-0.411	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/D	0.8738	likely_pathogenic	0.8524	pathogenic	-0.476	Destabilizing	0.994	D	0.611	neutral	None	None	None	None	N
K/E	0.4704	ambiguous	0.4424	ambiguous	-0.468	Destabilizing	0.767	D	0.298	neutral	N	0.461585369	None	None	N
K/F	0.9486	likely_pathogenic	0.9453	pathogenic	-0.74	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/G	0.5898	likely_pathogenic	0.5787	pathogenic	-0.528	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
K/H	0.5417	ambiguous	0.5483	ambiguous	-1.12	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
K/I	0.7533	likely_pathogenic	0.7303	pathogenic	0.207	Stabilizing	1.0	D	0.791	deleterious	N	0.48990434	None	None	N
K/L	0.6457	likely_pathogenic	0.6354	pathogenic	0.207	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	N
K/M	0.5064	ambiguous	0.489	ambiguous	0.457	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	N
K/N	0.7537	likely_pathogenic	0.724	pathogenic	-0.118	Destabilizing	0.999	D	0.678	prob.neutral	N	0.502202627	None	None	N
K/P	0.8247	likely_pathogenic	0.7996	pathogenic	0.064	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
K/Q	0.2165	likely_benign	0.222	benign	-0.468	Destabilizing	0.999	D	0.669	neutral	N	0.488350683	None	None	N
K/R	0.0776	likely_benign	0.0811	benign	-0.175	Destabilizing	0.996	D	0.475	neutral	N	0.470842357	None	None	N
K/S	0.6131	likely_pathogenic	0.5952	pathogenic	-0.639	Destabilizing	0.997	D	0.519	neutral	None	None	None	None	N
K/T	0.4766	ambiguous	0.4385	ambiguous	-0.48	Destabilizing	0.999	D	0.673	neutral	N	0.51659329	None	None	N
K/V	0.616	likely_pathogenic	0.595	pathogenic	0.064	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/W	0.9222	likely_pathogenic	0.9202	pathogenic	-0.681	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/Y	0.8635	likely_pathogenic	0.8596	pathogenic	-0.257	Destabilizing	1.0	D	0.759	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.