TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33643	101152;101153;101154	chr2:178535688;178535687;178535686	chr2:179400415;179400414;179400413
N2AB	32002	96229;96230;96231	chr2:178535688;178535687;178535686	chr2:179400415;179400414;179400413
N2A	31075	93448;93449;93450	chr2:178535688;178535687;178535686	chr2:179400415;179400414;179400413
N2B	24578	73957;73958;73959	chr2:178535688;178535687;178535686	chr2:179400415;179400414;179400413
Novex-1	24703	74332;74333;74334	chr2:178535688;178535687;178535686	chr2:179400415;179400414;179400413
Novex-2	24770	74533;74534;74535	chr2:178535688;178535687;178535686	chr2:179400415;179400414;179400413
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-159
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.2733
• 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/K	None	None	0.998	N	0.409	0.391	0.335414705075	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-05	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	0.6761	likely_pathogenic	0.5475	ambiguous	-0.643	Destabilizing	0.999	D	0.479	neutral	None	None	None	None	N
Q/C	0.9775	likely_pathogenic	0.9286	pathogenic	-0.058	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
Q/D	0.9011	likely_pathogenic	0.7232	pathogenic	-0.42	Destabilizing	0.998	D	0.482	neutral	None	None	None	None	N
Q/E	0.3249	likely_benign	0.1602	benign	-0.34	Destabilizing	0.995	D	0.333	neutral	N	0.497925463	None	None	N
Q/F	0.9874	likely_pathogenic	0.9643	pathogenic	-0.409	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
Q/G	0.8241	likely_pathogenic	0.7172	pathogenic	-0.978	Destabilizing	0.999	D	0.573	neutral	None	None	None	None	N
Q/H	0.736	likely_pathogenic	0.4736	ambiguous	-0.864	Destabilizing	0.999	D	0.631	neutral	N	0.510529401	None	None	N
Q/I	0.8974	likely_pathogenic	0.7931	pathogenic	0.2	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
Q/K	0.5193	ambiguous	0.2259	benign	-0.275	Destabilizing	0.998	D	0.409	neutral	N	0.475432606	None	None	N
Q/L	0.6738	likely_pathogenic	0.4941	ambiguous	0.2	Stabilizing	0.998	D	0.573	neutral	N	0.510009326	None	None	N
Q/M	0.795	likely_pathogenic	0.6993	pathogenic	0.639	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	N
Q/N	0.6834	likely_pathogenic	0.5282	ambiguous	-0.805	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
Q/P	0.9804	likely_pathogenic	0.9504	pathogenic	-0.05	Destabilizing	0.999	D	0.732	prob.delet.	D	0.529461879	None	None	N
Q/R	0.519	ambiguous	0.2459	benign	-0.22	Destabilizing	0.997	D	0.462	neutral	N	0.46381289	None	None	N
Q/S	0.5393	ambiguous	0.4401	ambiguous	-0.915	Destabilizing	0.999	D	0.431	neutral	None	None	None	None	N
Q/T	0.5383	ambiguous	0.3962	ambiguous	-0.641	Destabilizing	0.996	D	0.653	neutral	None	None	None	None	N
Q/V	0.7877	likely_pathogenic	0.6435	pathogenic	-0.05	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
Q/W	0.9885	likely_pathogenic	0.954	pathogenic	-0.263	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
Q/Y	0.9692	likely_pathogenic	0.8929	pathogenic	-0.042	Destabilizing	1.0	D	0.737	prob.delet.	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.