TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31012	93259;93260;93261	chr2:178548592;178548591;178548590	chr2:179413319;179413318;179413317
N2AB	29371	88336;88337;88338	chr2:178548592;178548591;178548590	chr2:179413319;179413318;179413317
N2A	28444	85555;85556;85557	chr2:178548592;178548591;178548590	chr2:179413319;179413318;179413317
N2B	21947	66064;66065;66066	chr2:178548592;178548591;178548590	chr2:179413319;179413318;179413317
Novex-1	22072	66439;66440;66441	chr2:178548592;178548591;178548590	chr2:179413319;179413318;179413317
Novex-2	22139	66640;66641;66642	chr2:178548592;178548591;178548590	chr2:179413319;179413318;179413317
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-150
• Domain position: 86
• Structural Position: 175
• Q(SASA): 0.302
• 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
K/E	None	None	0.999	N	0.625	0.493	0.354610295913	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88232E-05	0	0	0	0
K/I	rs1698136089	None	1.0	N	0.814	0.611	0.614323175037	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
K/I	rs1698136089	None	1.0	N	0.814	0.611	0.614323175037	gnomAD-4.0.0	6.57212E-06	None	None	None	None	N	None	0	6.55394E-05	None	0	0	None	0	0	0	0	0
K/N	None	None	1.0	D	0.765	0.329	0.235038932564	gnomAD-4.0.0	1.59112E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85806E-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
K/A	0.9518	likely_pathogenic	0.9535	pathogenic	-0.409	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
K/C	0.9596	likely_pathogenic	0.9577	pathogenic	-0.534	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/D	0.978	likely_pathogenic	0.9808	pathogenic	0.097	Stabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
K/E	0.8983	likely_pathogenic	0.9066	pathogenic	0.198	Stabilizing	0.999	D	0.625	neutral	N	0.518012734	None	None	N
K/F	0.9894	likely_pathogenic	0.9893	pathogenic	-0.11	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
K/G	0.9766	likely_pathogenic	0.9776	pathogenic	-0.759	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/H	0.6881	likely_pathogenic	0.6942	pathogenic	-1.022	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/I	0.9098	likely_pathogenic	0.9044	pathogenic	0.486	Stabilizing	1.0	D	0.814	deleterious	N	0.517956806	None	None	N
K/L	0.8875	likely_pathogenic	0.8779	pathogenic	0.486	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/M	0.8095	likely_pathogenic	0.7951	pathogenic	0.232	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
K/N	0.945	likely_pathogenic	0.9495	pathogenic	-0.326	Destabilizing	1.0	D	0.765	deleterious	D	0.528653802	None	None	N
K/P	0.9957	likely_pathogenic	0.9956	pathogenic	0.219	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/Q	0.5865	likely_pathogenic	0.6002	pathogenic	-0.381	Destabilizing	1.0	D	0.761	deleterious	D	0.529421806	None	None	N
K/R	0.1137	likely_benign	0.114	benign	-0.499	Destabilizing	0.999	D	0.58	neutral	N	0.4675867	None	None	N
K/S	0.958	likely_pathogenic	0.9609	pathogenic	-0.978	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
K/T	0.8105	likely_pathogenic	0.8124	pathogenic	-0.674	Destabilizing	1.0	D	0.791	deleterious	N	0.490383415	None	None	N
K/V	0.8831	likely_pathogenic	0.8752	pathogenic	0.219	Stabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
K/W	0.9699	likely_pathogenic	0.9723	pathogenic	-0.002	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/Y	0.9578	likely_pathogenic	0.9579	pathogenic	0.288	Stabilizing	1.0	D	0.789	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.