TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20737	62434;62435;62436	chr2:178589516;178589515;178589514	chr2:179454243;179454242;179454241
N2AB	19096	57511;57512;57513	chr2:178589516;178589515;178589514	chr2:179454243;179454242;179454241
N2A	18169	54730;54731;54732	chr2:178589516;178589515;178589514	chr2:179454243;179454242;179454241
N2B	11672	35239;35240;35241	chr2:178589516;178589515;178589514	chr2:179454243;179454242;179454241
Novex-1	11797	35614;35615;35616	chr2:178589516;178589515;178589514	chr2:179454243;179454242;179454241
Novex-2	11864	35815;35816;35817	chr2:178589516;178589515;178589514	chr2:179454243;179454242;179454241
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-38
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.1686
• 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
Q/P	None	None	0.966	N	0.36	0.535	0.387202362727	gnomAD-4.0.0	1.5921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85923E-06	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
Q/A	0.4096	ambiguous	0.4186	ambiguous	-0.685	Destabilizing	0.842	D	0.327	neutral	None	None	None	None	N
Q/C	0.8022	likely_pathogenic	0.8585	pathogenic	-0.102	Destabilizing	0.998	D	0.487	neutral	None	None	None	None	N
Q/D	0.5406	ambiguous	0.5748	pathogenic	-0.795	Destabilizing	0.842	D	0.331	neutral	None	None	None	None	N
Q/E	0.127	likely_benign	0.1411	benign	-0.604	Destabilizing	0.454	N	0.388	neutral	N	0.470244925	None	None	N
Q/F	0.8914	likely_pathogenic	0.9185	pathogenic	-0.185	Destabilizing	0.974	D	0.456	neutral	None	None	None	None	N
Q/G	0.4852	ambiguous	0.508	ambiguous	-1.109	Destabilizing	0.842	D	0.369	neutral	None	None	None	None	N
Q/H	0.3403	ambiguous	0.4239	ambiguous	-0.669	Destabilizing	0.012	N	0.221	neutral	N	0.45835585	None	None	N
Q/I	0.7695	likely_pathogenic	0.8099	pathogenic	0.437	Stabilizing	0.974	D	0.468	neutral	None	None	None	None	N
Q/K	0.1525	likely_benign	0.1693	benign	-0.34	Destabilizing	0.012	N	0.218	neutral	N	0.470071566	None	None	N
Q/L	0.3648	ambiguous	0.4246	ambiguous	0.437	Stabilizing	0.801	D	0.409	neutral	N	0.495892731	None	None	N
Q/M	0.4848	ambiguous	0.5361	ambiguous	0.656	Stabilizing	0.991	D	0.359	neutral	None	None	None	None	N
Q/N	0.3783	ambiguous	0.4049	ambiguous	-1.099	Destabilizing	0.842	D	0.335	neutral	None	None	None	None	N
Q/P	0.9649	likely_pathogenic	0.9611	pathogenic	0.093	Stabilizing	0.966	D	0.36	neutral	N	0.482902901	None	None	N
Q/R	0.207	likely_benign	0.2463	benign	-0.362	Destabilizing	0.669	D	0.387	neutral	N	0.451696449	None	None	N
Q/S	0.3946	ambiguous	0.3752	ambiguous	-1.26	Destabilizing	0.842	D	0.309	neutral	None	None	None	None	N
Q/T	0.3669	ambiguous	0.3787	ambiguous	-0.859	Destabilizing	0.842	D	0.387	neutral	None	None	None	None	N
Q/V	0.5505	ambiguous	0.6123	pathogenic	0.093	Stabilizing	0.974	D	0.389	neutral	None	None	None	None	N
Q/W	0.8657	likely_pathogenic	0.92	pathogenic	-0.131	Destabilizing	0.998	D	0.454	neutral	None	None	None	None	N
Q/Y	0.7253	likely_pathogenic	0.8126	pathogenic	0.16	Stabilizing	0.949	D	0.359	neutral	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.