TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28271	85036;85037;85038	chr2:178561321;178561320;178561319	chr2:179426048;179426047;179426046
N2AB	26630	80113;80114;80115	chr2:178561321;178561320;178561319	chr2:179426048;179426047;179426046
N2A	25703	77332;77333;77334	chr2:178561321;178561320;178561319	chr2:179426048;179426047;179426046
N2B	19206	57841;57842;57843	chr2:178561321;178561320;178561319	chr2:179426048;179426047;179426046
Novex-1	19331	58216;58217;58218	chr2:178561321;178561320;178561319	chr2:179426048;179426047;179426046
Novex-2	19398	58417;58418;58419	chr2:178561321;178561320;178561319	chr2:179426048;179426047;179426046
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-94
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1312
• 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/F	None	None	1.0	D	0.733	0.514	0.698486972665	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
L/A	0.9661	likely_pathogenic	0.976	pathogenic	-2.618	Highly Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
L/C	0.9237	likely_pathogenic	0.95	pathogenic	-1.251	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9998	pathogenic	-3.09	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
L/E	0.9974	likely_pathogenic	0.9981	pathogenic	-2.78	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
L/F	0.7414	likely_pathogenic	0.7915	pathogenic	-1.523	Destabilizing	1.0	D	0.733	prob.delet.	D	0.546233292	None	None	N
L/G	0.9957	likely_pathogenic	0.9968	pathogenic	-3.17	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/H	0.9956	likely_pathogenic	0.997	pathogenic	-2.908	Highly Destabilizing	1.0	D	0.847	deleterious	D	0.570377935	None	None	N
L/I	0.1207	likely_benign	0.1379	benign	-0.934	Destabilizing	0.999	D	0.531	neutral	D	0.530667026	None	None	N
L/K	0.9954	likely_pathogenic	0.9963	pathogenic	-1.813	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
L/M	0.3013	likely_benign	0.3626	ambiguous	-1.027	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
L/N	0.9982	likely_pathogenic	0.9987	pathogenic	-2.556	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
L/P	0.9982	likely_pathogenic	0.9984	pathogenic	-1.491	Destabilizing	1.0	D	0.904	deleterious	D	0.570377935	None	None	N
L/Q	0.99	likely_pathogenic	0.9928	pathogenic	-2.156	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/R	0.9913	likely_pathogenic	0.9931	pathogenic	-2.037	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.570377935	None	None	N
L/S	0.9958	likely_pathogenic	0.9973	pathogenic	-2.924	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/T	0.974	likely_pathogenic	0.9824	pathogenic	-2.465	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/V	0.1561	likely_benign	0.2039	benign	-1.491	Destabilizing	0.999	D	0.551	neutral	N	0.474312208	None	None	N
L/W	0.9825	likely_pathogenic	0.9894	pathogenic	-1.785	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
L/Y	0.9868	likely_pathogenic	0.9914	pathogenic	-1.697	Destabilizing	1.0	D	0.785	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.