TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31856	95791;95792;95793	chr2:178545544;178545543;178545542	chr2:179410271;179410270;179410269
N2AB	30215	90868;90869;90870	chr2:178545544;178545543;178545542	chr2:179410271;179410270;179410269
N2A	29288	88087;88088;88089	chr2:178545544;178545543;178545542	chr2:179410271;179410270;179410269
N2B	22791	68596;68597;68598	chr2:178545544;178545543;178545542	chr2:179410271;179410270;179410269
Novex-1	22916	68971;68972;68973	chr2:178545544;178545543;178545542	chr2:179410271;179410270;179410269
Novex-2	22983	69172;69173;69174	chr2:178545544;178545543;178545542	chr2:179410271;179410270;179410269
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-120
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.4625
• 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
R/C	rs72648261	-0.533	1.0	N	0.763	0.46	None	gnomAD-2.1.1	2.14E-05	None	None	None	None	N	None	1.23987E-04	0	None	0	1.02428E-04	None	3.27E-05	None	0	0	0
R/C	rs72648261	-0.533	1.0	N	0.763	0.46	None	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	1.20691E-04	0	0	0	1.92976E-04	None	0	0	0	0	0
R/C	rs72648261	-0.533	1.0	N	0.763	0.46	None	gnomAD-4.0.0	1.30146E-05	None	None	None	None	N	None	1.33529E-04	0	None	0	2.22836E-05	None	0	0	1.69532E-06	8.78484E-05	0
R/G	rs72648261	None	1.0	N	0.697	0.388	0.396645960531	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/G	rs72648261	None	1.0	N	0.697	0.388	0.396645960531	gnomAD-4.0.0	1.23949E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69532E-06	0	0
R/H	rs876658093	-1.439	1.0	N	0.761	0.44	0.412328234245	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	1.77E-05	0
R/H	rs876658093	-1.439	1.0	N	0.761	0.44	0.412328234245	gnomAD-4.0.0	1.43691E-05	None	None	None	None	N	None	0	0	None	0	2.51915E-05	None	0	0	1.25934E-05	1.15937E-05	8.28391E-05
R/L	None	None	1.0	N	0.697	0.483	0.426670027402	gnomAD-4.0.0	6.84244E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99528E-07	0	0
R/P	None	None	1.0	N	0.728	0.448	0.448498829774	gnomAD-4.0.0	1.36849E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79906E-06	0	0
R/S	None	-0.953	1.0	N	0.764	0.347	0.384419519794	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.65344E-04

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
R/A	0.8594	likely_pathogenic	0.8642	pathogenic	-1.022	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
R/C	0.5004	ambiguous	0.4895	ambiguous	-0.995	Destabilizing	1.0	D	0.763	deleterious	N	0.516744781	None	None	N
R/D	0.9827	likely_pathogenic	0.9849	pathogenic	-0.298	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
R/E	0.8936	likely_pathogenic	0.8952	pathogenic	-0.172	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
R/F	0.9589	likely_pathogenic	0.9611	pathogenic	-0.851	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
R/G	0.8693	likely_pathogenic	0.8721	pathogenic	-1.338	Destabilizing	1.0	D	0.697	prob.neutral	N	0.478129961	None	None	N
R/H	0.3833	ambiguous	0.3857	ambiguous	-1.571	Destabilizing	1.0	D	0.761	deleterious	N	0.486951371	None	None	N
R/I	0.8014	likely_pathogenic	0.8005	pathogenic	-0.166	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
R/K	0.2321	likely_benign	0.2465	benign	-1.166	Destabilizing	0.998	D	0.542	neutral	None	None	None	None	N
R/L	0.761	likely_pathogenic	0.7404	pathogenic	-0.166	Destabilizing	1.0	D	0.697	prob.neutral	N	0.47838345	None	None	N
R/M	0.8099	likely_pathogenic	0.8106	pathogenic	-0.424	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
R/N	0.9595	likely_pathogenic	0.9626	pathogenic	-0.598	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
R/P	0.8411	likely_pathogenic	0.8451	pathogenic	-0.431	Destabilizing	1.0	D	0.728	prob.delet.	N	0.49121763	None	None	N
R/Q	0.3279	likely_benign	0.308	benign	-0.767	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
R/S	0.9427	likely_pathogenic	0.9411	pathogenic	-1.388	Destabilizing	1.0	D	0.764	deleterious	N	0.510032677	None	None	N
R/T	0.7989	likely_pathogenic	0.8093	pathogenic	-1.081	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
R/V	0.8075	likely_pathogenic	0.805	pathogenic	-0.431	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
R/W	0.6618	likely_pathogenic	0.6494	pathogenic	-0.466	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
R/Y	0.8887	likely_pathogenic	0.8903	pathogenic	-0.188	Destabilizing	1.0	D	0.752	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.