TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32381	97366;97367;97368	chr2:178542713;178542712;178542711	chr2:179407440;179407439;179407438
N2AB	30740	92443;92444;92445	chr2:178542713;178542712;178542711	chr2:179407440;179407439;179407438
N2A	29813	89662;89663;89664	chr2:178542713;178542712;178542711	chr2:179407440;179407439;179407438
N2B	23316	70171;70172;70173	chr2:178542713;178542712;178542711	chr2:179407440;179407439;179407438
Novex-1	23441	70546;70547;70548	chr2:178542713;178542712;178542711	chr2:179407440;179407439;179407438
Novex-2	23508	70747;70748;70749	chr2:178542713;178542712;178542711	chr2:179407440;179407439;179407438
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-154
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.112
• 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
L/M	None	None	0.984	N	0.757	0.261	0.479286488449	gnomAD-4.0.0	6.84212E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99481E-07	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
L/A	0.6469	likely_pathogenic	0.5442	ambiguous	-2.112	Highly Destabilizing	0.702	D	0.7	prob.neutral	None	None	None	None	N
L/C	0.7674	likely_pathogenic	0.6956	pathogenic	-1.625	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
L/D	0.9984	likely_pathogenic	0.9972	pathogenic	-1.779	Destabilizing	0.996	D	0.821	deleterious	None	None	None	None	N
L/E	0.9914	likely_pathogenic	0.9853	pathogenic	-1.738	Destabilizing	0.988	D	0.821	deleterious	None	None	None	None	N
L/F	0.8189	likely_pathogenic	0.7207	pathogenic	-1.572	Destabilizing	0.984	D	0.764	deleterious	D	0.530576599	None	None	N
L/G	0.9195	likely_pathogenic	0.8631	pathogenic	-2.491	Highly Destabilizing	0.988	D	0.82	deleterious	None	None	None	None	N
L/H	0.9879	likely_pathogenic	0.9796	pathogenic	-1.705	Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	N
L/I	0.1853	likely_benign	0.1551	benign	-1.111	Destabilizing	0.702	D	0.601	neutral	None	None	None	None	N
L/K	0.9904	likely_pathogenic	0.9859	pathogenic	-1.501	Destabilizing	0.988	D	0.798	deleterious	None	None	None	None	N
L/M	0.2812	likely_benign	0.2114	benign	-0.958	Destabilizing	0.984	D	0.757	deleterious	N	0.487209824	None	None	N
L/N	0.9838	likely_pathogenic	0.9767	pathogenic	-1.412	Destabilizing	0.996	D	0.817	deleterious	None	None	None	None	N
L/P	0.9962	likely_pathogenic	0.9937	pathogenic	-1.416	Destabilizing	0.996	D	0.819	deleterious	None	None	None	None	N
L/Q	0.9605	likely_pathogenic	0.9339	pathogenic	-1.577	Destabilizing	0.996	D	0.787	deleterious	None	None	None	None	N
L/R	0.9775	likely_pathogenic	0.9662	pathogenic	-0.911	Destabilizing	0.996	D	0.785	deleterious	None	None	None	None	N
L/S	0.9505	likely_pathogenic	0.9059	pathogenic	-2.099	Highly Destabilizing	0.984	D	0.784	deleterious	N	0.51181748	None	None	N
L/T	0.8194	likely_pathogenic	0.7441	pathogenic	-1.929	Destabilizing	0.919	D	0.737	prob.delet.	None	None	None	None	N
L/V	0.1468	likely_benign	0.1256	benign	-1.416	Destabilizing	0.011	N	0.306	neutral	N	0.392272504	None	None	N
L/W	0.9737	likely_pathogenic	0.9533	pathogenic	-1.656	Destabilizing	0.999	D	0.765	deleterious	D	0.530923316	None	None	N
L/Y	0.9727	likely_pathogenic	0.9548	pathogenic	-1.431	Destabilizing	0.996	D	0.777	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.