TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29513	88762;88763;88764	chr2:178554922;178554921;178554920	chr2:179419649;179419648;179419647
N2AB	27872	83839;83840;83841	chr2:178554922;178554921;178554920	chr2:179419649;179419648;179419647
N2A	26945	81058;81059;81060	chr2:178554922;178554921;178554920	chr2:179419649;179419648;179419647
N2B	20448	61567;61568;61569	chr2:178554922;178554921;178554920	chr2:179419649;179419648;179419647
Novex-1	20573	61942;61943;61944	chr2:178554922;178554921;178554920	chr2:179419649;179419648;179419647
Novex-2	20640	62143;62144;62145	chr2:178554922;178554921;178554920	chr2:179419649;179419648;179419647
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-146
• Domain position: 70
• Structural Position: 156
• Q(SASA): 0.0918
• 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
L/S	rs1318031463	-2.76	0.999	N	0.844	0.521	0.674404827817	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
L/S	rs1318031463	-2.76	0.999	N	0.844	0.521	0.674404827817	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85785E-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
L/A	0.956	likely_pathogenic	0.9441	pathogenic	-2.545	Highly Destabilizing	0.997	D	0.705	prob.neutral	None	None	None	None	N
L/C	0.9199	likely_pathogenic	0.9021	pathogenic	-1.819	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9993	pathogenic	-2.964	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/E	0.9954	likely_pathogenic	0.9943	pathogenic	-2.721	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/F	0.7371	likely_pathogenic	0.6867	pathogenic	-1.519	Destabilizing	0.999	D	0.812	deleterious	N	0.476442942	None	None	N
L/G	0.9896	likely_pathogenic	0.9864	pathogenic	-3.108	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/H	0.9935	likely_pathogenic	0.9913	pathogenic	-2.628	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
L/I	0.1309	likely_benign	0.1197	benign	-0.905	Destabilizing	0.981	D	0.669	neutral	N	0.456939193	None	None	N
L/K	0.9911	likely_pathogenic	0.9885	pathogenic	-1.897	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/M	0.2828	likely_benign	0.2451	benign	-0.901	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
L/N	0.9965	likely_pathogenic	0.9956	pathogenic	-2.309	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/P	0.9962	likely_pathogenic	0.9946	pathogenic	-1.434	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/Q	0.9846	likely_pathogenic	0.9789	pathogenic	-2.136	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/R	0.985	likely_pathogenic	0.9812	pathogenic	-1.671	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/S	0.9962	likely_pathogenic	0.9949	pathogenic	-2.99	Highly Destabilizing	0.999	D	0.844	deleterious	N	0.477963879	None	None	N
L/T	0.9783	likely_pathogenic	0.9728	pathogenic	-2.598	Highly Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
L/V	0.1968	likely_benign	0.1781	benign	-1.434	Destabilizing	0.767	D	0.412	neutral	N	0.440892305	None	None	N
L/W	0.9694	likely_pathogenic	0.9563	pathogenic	-1.96	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
L/Y	0.9728	likely_pathogenic	0.9614	pathogenic	-1.656	Destabilizing	1.0	D	0.791	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.