TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1644	5155;5156;5157	chr2:178776934;178776933;178776932	chr2:179641661;179641660;179641659
N2AB	1644	5155;5156;5157	chr2:178776934;178776933;178776932	chr2:179641661;179641660;179641659
N2A	1644	5155;5156;5157	chr2:178776934;178776933;178776932	chr2:179641661;179641660;179641659
N2B	1598	5017;5018;5019	chr2:178776934;178776933;178776932	chr2:179641661;179641660;179641659
Novex-1	1598	5017;5018;5019	chr2:178776934;178776933;178776932	chr2:179641661;179641660;179641659
Novex-2	1598	5017;5018;5019	chr2:178776934;178776933;178776932	chr2:179641661;179641660;179641659
Novex-3	1644	5155;5156;5157	chr2:178776934;178776933;178776932	chr2:179641661;179641660;179641659

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-7
• Domain position: 89
• Structural Position: 173
• Q(SASA): 0.5565
• 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	rs2092286862	None	0.961	N	0.617	0.544	0.324986149311	gnomAD-4.0.0	1.59208E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85845E-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	0.9774	likely_pathogenic	0.9703	pathogenic	-0.984	Destabilizing	0.97	D	0.66	neutral	None	None	None	None	N
K/C	0.9836	likely_pathogenic	0.9749	pathogenic	-1.026	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
K/D	0.9971	likely_pathogenic	0.9958	pathogenic	-0.921	Destabilizing	0.996	D	0.711	prob.delet.	None	None	None	None	N
K/E	0.968	likely_pathogenic	0.9547	pathogenic	-0.75	Destabilizing	0.961	D	0.617	neutral	N	0.502183208	None	None	N
K/F	0.9914	likely_pathogenic	0.9881	pathogenic	-0.603	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
K/G	0.9892	likely_pathogenic	0.9859	pathogenic	-1.404	Destabilizing	0.985	D	0.693	prob.neutral	None	None	None	None	N
K/H	0.8431	likely_pathogenic	0.7964	pathogenic	-1.784	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
K/I	0.9568	likely_pathogenic	0.9455	pathogenic	0.144	Stabilizing	0.998	D	0.744	deleterious	D	0.555401178	None	None	N
K/L	0.9255	likely_pathogenic	0.9007	pathogenic	0.144	Stabilizing	0.97	D	0.693	prob.neutral	None	None	None	None	N
K/M	0.8829	likely_pathogenic	0.848	pathogenic	0.104	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
K/N	0.987	likely_pathogenic	0.9812	pathogenic	-1.123	Destabilizing	0.994	D	0.637	neutral	N	0.509793035	None	None	N
K/P	0.9929	likely_pathogenic	0.9926	pathogenic	-0.204	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
K/Q	0.7743	likely_pathogenic	0.6965	pathogenic	-1.091	Destabilizing	0.989	D	0.659	neutral	N	0.509452657	None	None	N
K/R	0.1382	likely_benign	0.1146	benign	-0.93	Destabilizing	0.031	N	0.199	neutral	N	0.481994033	None	None	N
K/S	0.9875	likely_pathogenic	0.9832	pathogenic	-1.74	Destabilizing	0.985	D	0.619	neutral	None	None	None	None	N
K/T	0.9501	likely_pathogenic	0.9329	pathogenic	-1.337	Destabilizing	0.98	D	0.699	prob.neutral	N	0.504696727	None	None	N
K/V	0.9415	likely_pathogenic	0.9275	pathogenic	-0.204	Destabilizing	0.996	D	0.695	prob.neutral	None	None	None	None	N
K/W	0.9851	likely_pathogenic	0.9784	pathogenic	-0.532	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
K/Y	0.9771	likely_pathogenic	0.9661	pathogenic	-0.201	Destabilizing	0.999	D	0.755	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.