TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21096	63511;63512;63513	chr2:178588121;178588120;178588119	chr2:179452848;179452847;179452846
N2AB	19455	58588;58589;58590	chr2:178588121;178588120;178588119	chr2:179452848;179452847;179452846
N2A	18528	55807;55808;55809	chr2:178588121;178588120;178588119	chr2:179452848;179452847;179452846
N2B	12031	36316;36317;36318	chr2:178588121;178588120;178588119	chr2:179452848;179452847;179452846
Novex-1	12156	36691;36692;36693	chr2:178588121;178588120;178588119	chr2:179452848;179452847;179452846
Novex-2	12223	36892;36893;36894	chr2:178588121;178588120;178588119	chr2:179452848;179452847;179452846
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-41
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1753
• 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
I/N	rs558727238	-1.985	0.999	D	0.823	0.55	0.864698151722	gnomAD-2.1.1	1.65271E-04	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	1.30787E-03	None	0	0	0
I/N	rs558727238	-1.985	0.999	D	0.823	0.55	0.864698151722	gnomAD-3.1.2	4.6E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	1.45108E-03	0
I/N	rs558727238	-1.985	0.999	D	0.823	0.55	0.864698151722	1000 genomes	3.99361E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	2E-03	None
I/N	rs558727238	-1.985	0.999	D	0.823	0.55	0.864698151722	gnomAD-4.0.0	7.37809E-05	None	None	None	None	I	None	0	3.33611E-05	None	0	0	None	0	0	8.47968E-07	1.24154E-03	4.80492E-05
I/V	rs568922646	-1.483	0.198	N	0.249	0.122	0.474564258015	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
I/V	rs568922646	-1.483	0.198	N	0.249	0.122	0.474564258015	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	2.41E-05	6.56E-05	0	0	0	None	0	0	0	0	0
I/V	rs568922646	-1.483	0.198	N	0.249	0.122	0.474564258015	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
I/V	rs568922646	-1.483	0.198	N	0.249	0.122	0.474564258015	gnomAD-4.0.0	1.31422E-05	None	None	None	None	I	None	2.40535E-05	6.54707E-05	None	0	0	None	0	0	0	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
I/A	0.9669	likely_pathogenic	0.9496	pathogenic	-2.181	Highly Destabilizing	0.983	D	0.652	neutral	None	None	None	None	I
I/C	0.9778	likely_pathogenic	0.9672	pathogenic	-1.169	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
I/D	0.9983	likely_pathogenic	0.9973	pathogenic	-2.046	Highly Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	I
I/E	0.9943	likely_pathogenic	0.9914	pathogenic	-1.968	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	I
I/F	0.912	likely_pathogenic	0.9039	pathogenic	-1.447	Destabilizing	0.997	D	0.774	deleterious	D	0.53079102	None	None	I
I/G	0.996	likely_pathogenic	0.9934	pathogenic	-2.586	Highly Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	I
I/H	0.9961	likely_pathogenic	0.9938	pathogenic	-1.849	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
I/K	0.992	likely_pathogenic	0.9871	pathogenic	-1.661	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	I
I/L	0.3436	ambiguous	0.314	benign	-1.084	Destabilizing	0.798	D	0.479	neutral	D	0.522583474	None	None	I
I/M	0.5493	ambiguous	0.521	ambiguous	-0.716	Destabilizing	0.997	D	0.735	prob.delet.	N	0.521805026	None	None	I
I/N	0.9724	likely_pathogenic	0.9539	pathogenic	-1.587	Destabilizing	0.999	D	0.823	deleterious	D	0.534339873	None	None	I
I/P	0.9792	likely_pathogenic	0.9641	pathogenic	-1.424	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	I
I/Q	0.9931	likely_pathogenic	0.9889	pathogenic	-1.693	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	I
I/R	0.9893	likely_pathogenic	0.9826	pathogenic	-1.054	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	I
I/S	0.9801	likely_pathogenic	0.9662	pathogenic	-2.198	Highly Destabilizing	0.997	D	0.777	deleterious	D	0.54493571	None	None	I
I/T	0.9493	likely_pathogenic	0.9295	pathogenic	-2.005	Highly Destabilizing	0.978	D	0.77	deleterious	D	0.522058515	None	None	I
I/V	0.0893	likely_benign	0.0888	benign	-1.424	Destabilizing	0.198	N	0.249	neutral	N	0.474578883	None	None	I
I/W	0.9977	likely_pathogenic	0.9974	pathogenic	-1.669	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
I/Y	0.9892	likely_pathogenic	0.9844	pathogenic	-1.44	Destabilizing	0.999	D	0.78	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.