TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6222	18889;18890;18891	chr2:178729492;178729491;178729490	chr2:179594219;179594218;179594217
N2AB	5905	17938;17939;17940	chr2:178729492;178729491;178729490	chr2:179594219;179594218;179594217
N2A	4978	15157;15158;15159	chr2:178729492;178729491;178729490	chr2:179594219;179594218;179594217
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-46
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.0772
• 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
V/A	None	None	0.994	N	0.655	0.537	0.689150956925	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.4316	ambiguous	0.4627	ambiguous	-1.73	Destabilizing	0.994	D	0.655	neutral	N	0.510788478	None	None	N
V/C	0.9068	likely_pathogenic	0.9358	pathogenic	-1.02	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
V/D	0.9777	likely_pathogenic	0.9737	pathogenic	-2.39	Highly Destabilizing	0.999	D	0.822	deleterious	D	0.623840275	None	None	N
V/E	0.9551	likely_pathogenic	0.9498	pathogenic	-2.091	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/F	0.5514	ambiguous	0.5285	ambiguous	-0.94	Destabilizing	0.997	D	0.788	deleterious	D	0.56174159	None	None	N
V/G	0.5553	ambiguous	0.5819	pathogenic	-2.333	Highly Destabilizing	0.999	D	0.829	deleterious	D	0.591801553	None	None	N
V/H	0.9846	likely_pathogenic	0.9857	pathogenic	-2.337	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/I	0.0994	likely_benign	0.1074	benign	-0.005	Destabilizing	0.543	D	0.239	neutral	D	0.525600428	None	None	N
V/K	0.9708	likely_pathogenic	0.9683	pathogenic	-1.134	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
V/L	0.3378	likely_benign	0.4212	ambiguous	-0.005	Destabilizing	0.217	N	0.283	neutral	D	0.573099844	None	None	N
V/M	0.3573	ambiguous	0.3791	ambiguous	-0.159	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
V/N	0.9411	likely_pathogenic	0.9456	pathogenic	-1.7	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/P	0.9744	likely_pathogenic	0.9774	pathogenic	-0.557	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
V/Q	0.9589	likely_pathogenic	0.959	pathogenic	-1.36	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
V/R	0.9539	likely_pathogenic	0.9531	pathogenic	-1.355	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/S	0.7864	likely_pathogenic	0.8123	pathogenic	-2.27	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/T	0.6577	likely_pathogenic	0.6778	pathogenic	-1.808	Destabilizing	0.996	D	0.689	prob.neutral	None	None	None	None	N
V/W	0.9813	likely_pathogenic	0.9808	pathogenic	-1.541	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
V/Y	0.9263	likely_pathogenic	0.9185	pathogenic	-1.094	Destabilizing	1.0	D	0.767	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.