TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32720	98383;98384;98385	chr2:178539907;178539906;178539905	chr2:179404634;179404633;179404632
N2AB	31079	93460;93461;93462	chr2:178539907;178539906;178539905	chr2:179404634;179404633;179404632
N2A	30152	90679;90680;90681	chr2:178539907;178539906;178539905	chr2:179404634;179404633;179404632
N2B	23655	71188;71189;71190	chr2:178539907;178539906;178539905	chr2:179404634;179404633;179404632
Novex-1	23780	71563;71564;71565	chr2:178539907;178539906;178539905	chr2:179404634;179404633;179404632
Novex-2	23847	71764;71765;71766	chr2:178539907;178539906;178539905	chr2:179404634;179404633;179404632
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-155
• Domain position: 13
• Structural Position: 25
• Q(SASA): 0.2531
• 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
G/D	None	None	1.0	N	0.776	0.429	0.148003135375	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
G/A	0.1994	likely_benign	0.1811	benign	-0.536	Destabilizing	0.998	D	0.541	neutral	N	0.467060186	None	None	I
G/C	0.3661	ambiguous	0.3169	benign	-0.952	Destabilizing	1.0	D	0.747	deleterious	N	0.481837637	None	None	I
G/D	0.6334	likely_pathogenic	0.5402	ambiguous	-0.715	Destabilizing	1.0	D	0.776	deleterious	N	0.409953322	None	None	I
G/E	0.6295	likely_pathogenic	0.5267	ambiguous	-0.819	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
G/F	0.8819	likely_pathogenic	0.8303	pathogenic	-0.967	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
G/H	0.7826	likely_pathogenic	0.7114	pathogenic	-0.969	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
G/I	0.7371	likely_pathogenic	0.6721	pathogenic	-0.354	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
G/K	0.8346	likely_pathogenic	0.761	pathogenic	-1.136	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
G/L	0.7889	likely_pathogenic	0.7179	pathogenic	-0.354	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
G/M	0.7152	likely_pathogenic	0.6322	pathogenic	-0.373	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
G/N	0.5598	ambiguous	0.4895	ambiguous	-0.79	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
G/P	0.9931	likely_pathogenic	0.9904	pathogenic	-0.375	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/Q	0.65	likely_pathogenic	0.5597	ambiguous	-1.005	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
G/R	0.727	likely_pathogenic	0.6424	pathogenic	-0.759	Destabilizing	1.0	D	0.802	deleterious	N	0.457901985	None	None	I
G/S	0.157	likely_benign	0.136	benign	-1.038	Destabilizing	0.991	D	0.606	neutral	N	0.417111368	None	None	I
G/T	0.3507	ambiguous	0.285	benign	-1.059	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
G/V	0.5603	ambiguous	0.4903	ambiguous	-0.375	Destabilizing	1.0	D	0.777	deleterious	N	0.467926977	None	None	I
G/W	0.8012	likely_pathogenic	0.7221	pathogenic	-1.228	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
G/Y	0.8107	likely_pathogenic	0.7367	pathogenic	-0.845	Destabilizing	1.0	D	0.749	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.