TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26079	78460;78461;78462	chr2:178567897;178567896;178567895	chr2:179432624;179432623;179432622
N2AB	24438	73537;73538;73539	chr2:178567897;178567896;178567895	chr2:179432624;179432623;179432622
N2A	23511	70756;70757;70758	chr2:178567897;178567896;178567895	chr2:179432624;179432623;179432622
N2B	17014	51265;51266;51267	chr2:178567897;178567896;178567895	chr2:179432624;179432623;179432622
Novex-1	17139	51640;51641;51642	chr2:178567897;178567896;178567895	chr2:179432624;179432623;179432622
Novex-2	17206	51841;51842;51843	chr2:178567897;178567896;178567895	chr2:179432624;179432623;179432622
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-77
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.3108
• 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
N/H	rs1331149411	None	0.412	N	0.453	0.082	0.229924730088	gnomAD-4.0.0	1.36859E-06	None	None	None	None	N	None	0	2.23614E-05	None	0	0	None	0	0	8.99588E-07	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
N/A	0.097	likely_benign	0.0986	benign	-1.069	Destabilizing	None	N	0.503	neutral	None	None	None	None	N
N/C	0.1428	likely_benign	0.1477	benign	-0.126	Destabilizing	0.482	N	0.67	prob.neutral	None	None	None	None	N
N/D	0.2421	likely_benign	0.257	benign	-0.332	Destabilizing	0.039	N	0.307	neutral	N	0.474839881	None	None	N
N/E	0.3782	ambiguous	0.3858	ambiguous	-0.268	Destabilizing	0.026	N	0.293	neutral	None	None	None	None	N
N/F	0.345	ambiguous	0.3531	ambiguous	-0.9	Destabilizing	0.482	N	0.758	deleterious	None	None	None	None	N
N/G	0.2042	likely_benign	0.2177	benign	-1.372	Destabilizing	0.012	N	0.411	neutral	None	None	None	None	N
N/H	0.1347	likely_benign	0.1406	benign	-0.991	Destabilizing	0.412	N	0.453	neutral	N	0.463969526	None	None	N
N/I	0.0617	likely_benign	0.0586	benign	-0.307	Destabilizing	0.02	N	0.619	neutral	N	0.374598316	None	None	N
N/K	0.2886	likely_benign	0.3037	benign	-0.278	Destabilizing	0.02	N	0.289	neutral	N	0.463449451	None	None	N
N/L	0.1024	likely_benign	0.0977	benign	-0.307	Destabilizing	0.012	N	0.633	neutral	None	None	None	None	N
N/M	0.1567	likely_benign	0.1541	benign	0.162	Stabilizing	0.482	N	0.622	neutral	None	None	None	None	N
N/P	0.1187	likely_benign	0.1148	benign	-0.533	Destabilizing	0.209	N	0.621	neutral	None	None	None	None	N
N/Q	0.2698	likely_benign	0.2825	benign	-0.911	Destabilizing	0.116	N	0.493	neutral	None	None	None	None	N
N/R	0.3516	ambiguous	0.374	ambiguous	-0.17	Destabilizing	0.116	N	0.463	neutral	None	None	None	None	N
N/S	0.0761	likely_benign	0.0787	benign	-0.901	Destabilizing	None	N	0.304	neutral	N	0.388143616	None	None	N
N/T	0.0707	likely_benign	0.0706	benign	-0.645	Destabilizing	None	N	0.235	neutral	N	0.364536038	None	None	N
N/V	0.0614	likely_benign	0.06	benign	-0.533	Destabilizing	None	N	0.479	neutral	None	None	None	None	N
N/W	0.7182	likely_pathogenic	0.7266	pathogenic	-0.594	Destabilizing	0.914	D	0.726	deleterious	None	None	None	None	N
N/Y	0.1425	likely_benign	0.1487	benign	-0.436	Destabilizing	0.412	N	0.685	prob.delet.	N	0.493252283	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.