TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3861	11806;11807;11808	chr2:178741652;178741651;178741650	chr2:179606379;179606378;179606377
N2AB	3544	10855;10856;10857	chr2:178741652;178741651;178741650	chr2:179606379;179606378;179606377
N2A	None	None	chr2:None	chr2:None
N2B	3498	10717;10718;10719	chr2:178741652;178741651;178741650	chr2:179606379;179606378;179606377
Novex-1	3623	11092;11093;11094	chr2:178741652;178741651;178741650	chr2:179606379;179606378;179606377
Novex-2	3690	11293;11294;11295	chr2:178741652;178741651;178741650	chr2:179606379;179606378;179606377
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-27
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.572
• 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
T/I	rs1214393200	0.003	0.015	N	0.22	0.121	None	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
T/I	rs1214393200	0.003	0.015	N	0.22	0.121	None	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
T/I	rs1214393200	0.003	0.015	N	0.22	0.121	None	gnomAD-4.0.0	6.57134E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47016E-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
T/A	0.0923	likely_benign	0.0924	benign	-0.446	Destabilizing	0.472	N	0.249	neutral	N	0.507628252	None	None	I
T/C	0.4116	ambiguous	0.4065	ambiguous	-0.596	Destabilizing	0.996	D	0.369	neutral	None	None	None	None	I
T/D	0.3017	likely_benign	0.3071	benign	0.359	Stabilizing	0.59	D	0.303	neutral	None	None	None	None	I
T/E	0.2085	likely_benign	0.2188	benign	0.349	Stabilizing	0.037	N	0.195	neutral	None	None	None	None	I
T/F	0.1739	likely_benign	0.1622	benign	-0.993	Destabilizing	0.91	D	0.387	neutral	None	None	None	None	I
T/G	0.3047	likely_benign	0.2924	benign	-0.58	Destabilizing	0.742	D	0.363	neutral	None	None	None	None	I
T/H	0.1876	likely_benign	0.1811	benign	-0.54	Destabilizing	0.996	D	0.376	neutral	None	None	None	None	I
T/I	0.1162	likely_benign	0.1022	benign	-0.196	Destabilizing	0.015	N	0.22	neutral	N	0.503671358	None	None	I
T/K	0.1476	likely_benign	0.1418	benign	-0.128	Destabilizing	0.009	N	0.195	neutral	None	None	None	None	I
T/L	0.0821	likely_benign	0.0771	benign	-0.196	Destabilizing	0.331	N	0.291	neutral	None	None	None	None	I
T/M	0.085	likely_benign	0.0827	benign	-0.496	Destabilizing	0.91	D	0.324	neutral	None	None	None	None	I
T/N	0.098	likely_benign	0.0949	benign	-0.27	Destabilizing	0.884	D	0.269	neutral	N	0.485860546	None	None	I
T/P	0.11	likely_benign	0.1103	benign	-0.253	Destabilizing	0.007	N	0.197	neutral	N	0.479486679	None	None	I
T/Q	0.1636	likely_benign	0.1677	benign	-0.295	Destabilizing	0.91	D	0.314	neutral	None	None	None	None	I
T/R	0.1231	likely_benign	0.1156	benign	0.098	Stabilizing	0.59	D	0.325	neutral	None	None	None	None	I
T/S	0.1083	likely_benign	0.1103	benign	-0.514	Destabilizing	0.684	D	0.271	neutral	N	0.488402889	None	None	I
T/V	0.1284	likely_benign	0.1208	benign	-0.253	Destabilizing	0.331	N	0.244	neutral	None	None	None	None	I
T/W	0.5414	ambiguous	0.5118	ambiguous	-1.084	Destabilizing	0.996	D	0.491	neutral	None	None	None	None	I
T/Y	0.2057	likely_benign	0.1933	benign	-0.732	Destabilizing	0.953	D	0.384	neutral	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.