TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1167	3724;3725;3726	chr2:178781145;178781144;178781143	chr2:179645872;179645871;179645870
N2AB	1167	3724;3725;3726	chr2:178781145;178781144;178781143	chr2:179645872;179645871;179645870
N2A	1167	3724;3725;3726	chr2:178781145;178781144;178781143	chr2:179645872;179645871;179645870
N2B	1121	3586;3587;3588	chr2:178781145;178781144;178781143	chr2:179645872;179645871;179645870
Novex-1	1121	3586;3587;3588	chr2:178781145;178781144;178781143	chr2:179645872;179645871;179645870
Novex-2	1121	3586;3587;3588	chr2:178781145;178781144;178781143	chr2:179645872;179645871;179645870
Novex-3	1167	3724;3725;3726	chr2:178781145;178781144;178781143	chr2:179645872;179645871;179645870

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-4
• Domain position: 86
• Structural Position: 169
• Q(SASA): 0.133
• 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
A/T	rs1248484876	None	0.946	N	0.735	0.429	0.349870743963	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs1248484876	None	0.946	N	0.735	0.429	0.349870743963	gnomAD-4.0.0	6.57125E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46985E-05	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
A/C	0.6806	likely_pathogenic	0.679	pathogenic	-0.839	Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	I
A/D	0.8431	likely_pathogenic	0.83	pathogenic	-0.752	Destabilizing	0.921	D	0.813	deleterious	None	None	None	None	I
A/E	0.7982	likely_pathogenic	0.8003	pathogenic	-0.672	Destabilizing	0.035	N	0.46	neutral	N	0.513213673	None	None	I
A/F	0.666	likely_pathogenic	0.7157	pathogenic	-0.633	Destabilizing	0.993	D	0.927	deleterious	None	None	None	None	I
A/G	0.3614	ambiguous	0.3527	ambiguous	-1.091	Destabilizing	0.834	D	0.589	neutral	N	0.519803724	None	None	I
A/H	0.8998	likely_pathogenic	0.9119	pathogenic	-1.309	Destabilizing	0.994	D	0.909	deleterious	None	None	None	None	I
A/I	0.5794	likely_pathogenic	0.634	pathogenic	0.203	Stabilizing	0.979	D	0.889	deleterious	None	None	None	None	I
A/K	0.9533	likely_pathogenic	0.9581	pathogenic	-0.807	Destabilizing	0.921	D	0.806	deleterious	None	None	None	None	I
A/L	0.521	ambiguous	0.5575	ambiguous	0.203	Stabilizing	0.87	D	0.772	deleterious	None	None	None	None	I
A/M	0.5639	ambiguous	0.6053	pathogenic	-0.013	Destabilizing	0.998	D	0.876	deleterious	None	None	None	None	I
A/N	0.8285	likely_pathogenic	0.8382	pathogenic	-0.77	Destabilizing	0.959	D	0.907	deleterious	None	None	None	None	I
A/P	0.9959	likely_pathogenic	0.9972	pathogenic	-0.057	Destabilizing	0.973	D	0.889	deleterious	D	0.55238336	None	None	I
A/Q	0.8283	likely_pathogenic	0.8359	pathogenic	-0.714	Destabilizing	0.921	D	0.889	deleterious	None	None	None	None	I
A/R	0.9034	likely_pathogenic	0.9144	pathogenic	-0.79	Destabilizing	0.959	D	0.889	deleterious	None	None	None	None	I
A/S	0.1792	likely_benign	0.1746	benign	-1.27	Destabilizing	0.716	D	0.581	neutral	N	0.465881456	None	None	I
A/T	0.1936	likely_benign	0.2036	benign	-1.05	Destabilizing	0.946	D	0.735	prob.delet.	N	0.478300395	None	None	I
A/V	0.2806	likely_benign	0.3085	benign	-0.057	Destabilizing	0.834	D	0.642	neutral	N	0.498641604	None	None	I
A/W	0.9682	likely_pathogenic	0.9728	pathogenic	-1.118	Destabilizing	0.998	D	0.893	deleterious	None	None	None	None	I
A/Y	0.8551	likely_pathogenic	0.8788	pathogenic	-0.582	Destabilizing	0.998	D	0.925	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.